{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T22:56:37Z","timestamp":1780440997919,"version":"3.54.1"},"reference-count":106,"publisher":"Springer Science and Business Media LLC","issue":"12","license":[{"start":{"date-parts":[[2020,10,19]],"date-time":"2020-10-19T00:00:00Z","timestamp":1603065600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2020,10,19]],"date-time":"2020-10-19T00:00:00Z","timestamp":1603065600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Comput Aided Mol Des"],"published-print":{"date-parts":[[2020,12]]},"DOI":"10.1007\/s10822-020-00355-5","type":"journal-article","created":{"date-parts":[[2020,10,19]],"date-time":"2020-10-19T02:02:36Z","timestamp":1603072956000},"page":"1289-1305","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Mutation-mediated influences on binding of anaplastic lymphoma kinase to crizotinib decoded by multiple replica Gaussian accelerated molecular dynamics"],"prefix":"10.1007","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1558-4398","authenticated-orcid":false,"given":"Jianzhong","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haibo","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laixue","family":"Pang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baohua","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,10,19]]},"reference":[{"issue":"18","key":"355_CR1","doi-asserted-by":"crossref","first-page":"2175","DOI":"10.1038\/sj.onc.1201062","volume":"14","author":"SW Morris","year":"1997","unstructured":"Morris SW, Naeve C, Mathew P, James PL, Kirstein MN, Cui X, Witte DP (1997) ALK, the chromosome 2 gene locus altered by the t(2;5) in non-Hodgkin\u2019s lymphoma, encodes a novel neural receptor tyrosine kinase that is highly related to leukocyte tyrosine kinase (LTK). Oncogene 14(18):2175\u20132188","journal-title":"Oncogene"},{"issue":"3","key":"355_CR2","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1038\/sj.npp.1301446","volume":"33","author":"JG Bilsland","year":"2008","unstructured":"Bilsland JG, Wheeldon A, Mead A, Znamenskiy P, Almond S, Waters KA, Thakur M, Beaumont V, Bonnert TP, Heavens R, Whiting P, McAllister G, Munoz-Sanjuan I (2008) Behavioral and neurochemical alterations in mice deficient in anaplastic lymphoma kinase suggest therapeutic potential for psychiatric indications. Neuropsychopharmacology 33(3):685\u2013700","journal-title":"Neuropsychopharmacology"},{"issue":"1","key":"355_CR3","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/nrc2291","volume":"8","author":"R Chiarle","year":"2008","unstructured":"Chiarle R, Voena C, Ambrogio C, Piva R, Inghirami G (2008) The anaplastic lymphoma kinase in the pathogenesis of cancer. Nat Rev Cancer 8(1):11\u201323","journal-title":"Nat Rev Cancer"},{"issue":"3","key":"355_CR4","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1586\/14737140.9.3.331","volume":"9","author":"TR Webb","year":"2009","unstructured":"Webb TR, Slavish J, George RE, Look AT, Xue L, Jiang Q, Cui X, Rentrop WB, Morris SW (2009) Anaplastic lymphoma kinase: role in cancer pathogenesis and small-molecule inhibitor development for therapy. Expert Rev Anticancer Ther 9(3):331\u2013356","journal-title":"Expert Rev Anticancer Ther"},{"issue":"4","key":"355_CR5","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1038\/sj.onc.1200849","volume":"14","author":"T Iwahara","year":"1997","unstructured":"Iwahara T, Fujimoto J, Wen D, Cupples R, Bucay N, Arakawa T, Mori S, Ratzkin B, Yamamoto T (1997) Molecular characterization of ALK, a receptor tyrosine kinase expressed specifically in the nervous system. Oncogene 14(4):439\u2013449","journal-title":"Oncogene"},{"issue":"5151","key":"355_CR6","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1126\/science.8122112","volume":"263","author":"S Morris","year":"1994","unstructured":"Morris S, Kirstein M, Valentine M, Dittmer K, Shapiro D, Saltman D, Look A (1994) Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin\u2019s lymphoma. Science 263(5151):1281\u20131284","journal-title":"Science"},{"issue":"8","key":"355_CR7","first-page":"561","volume":"40","author":"H Yu","year":"2011","unstructured":"Yu H, Huang J-x, Wang C-f, Shi D-r (2011) ALK-positive large B-cell lymphoma: report of a case. Zhonghua bing li xue za zhi 40(8):561\u2013562","journal-title":"Zhonghua bing li xue za zhi"},{"issue":"12","key":"355_CR8","first-page":"2776","volume":"59","author":"CA Griffin","year":"1999","unstructured":"Griffin CA, Hawkins AL, Dvorak C, Henkle C, Ellingham T, Perlman EJ (1999) Recurrent involvement of 2p23 in inflammatory myofibroblastic tumors. Cancer Res 59(12):2776\u20132780","journal-title":"Cancer Res"},{"issue":"12","key":"355_CR9","doi-asserted-by":"crossref","first-page":"2349","DOI":"10.1111\/j.1349-7006.2008.00972.x","volume":"99","author":"H Mano","year":"2008","unstructured":"Mano H (2008) Non-solid oncogenes in solid tumors: EML4\u2013ALK fusion genes in lung cancer. Cancer Sci 99(12):2349\u20132355","journal-title":"Cancer Sci"},{"issue":"8","key":"355_CR10","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.1158\/1078-0432.CCR-10-1591","volume":"17","author":"AT Shaw","year":"2011","unstructured":"Shaw AT, Solomon B (2011) Targeting anaplastic lymphoma kinase in lung cancer. Clin Cancer Res 17(8):2081\u20132086","journal-title":"Clin Cancer Res"},{"issue":"7153","key":"355_CR11","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1038\/nature05945","volume":"448","author":"M Soda","year":"2007","unstructured":"Soda M, Choi YL, Enomoto M, Takada S, Yamashita Y, Ishikawa S, Fujiwara S-i, Watanabe H, Kurashina K, Hatanaka H, Bando M, Ohno S, Ishikawa Y, Aburatani H, Niki T, Sohara Y, Sugiyama Y, Mano H (2007) Identification of the transforming EML4\u2013ALK fusion gene in non-small-cell lung cancer. Nature 448(7153):561\u2013566","journal-title":"Nature"},{"issue":"1","key":"355_CR12","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.phrs.2012.11.007","volume":"68","author":"R Roskoski","year":"2013","unstructured":"Roskoski R (2013) Anaplastic lymphoma kinase (ALK): Structure, oncogenic activation, and pharmacological inhibition. Pharmacol Res 68(1):68\u201394","journal-title":"Pharmacol Res"},{"issue":"11","key":"355_CR13","doi-asserted-by":"crossref","first-page":"4720","DOI":"10.1021\/jm500261q","volume":"57","author":"TW Johnson","year":"2014","unstructured":"Johnson TW, Richardson PF, Bailey S, Brooun A, Burke BJ, Collins MR, Cui JJ, Deal JG, Deng Y-L, Dinh D, Engstrom LD, He M, Hoffman J, Hoffman RL, Huang Q, Kania RS, Kath JC, Lam H, Lam JL, Le PT, Lingardo L, Liu W, McTigue M, Palmer CL, Sach NW, Smeal T, Smith GL, Stewart AE, Timofeevski S, Zhu H, Zhu J, Zou HY, Edwards MP (2014) Discovery of (10R)-7-Amino-12-fluoro-2,10,16-trimethyl-15-oxo-10,15,16,17-tetrahydro-2H-8,4-(metheno)pyrazolo[4,3-h][2,5,11]-benzoxadiazacyclotetradecine-3-carbonitrile (PF-06463922), a Macrocyclic Inhibitor of Anaplastic Lymphoma Kinase (ALK) and c-ros Oncogene 1 (ROS1) with Preclinical Brain Exposure and Broad-Spectrum Potency against ALK-Resistant Mutations. J Med Chem 57(11):4720\u20134744","journal-title":"J Med Chem"},{"issue":"3","key":"355_CR14","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1016\/j.bmcl.2015.11.049","volume":"26","author":"P-Y Michellys","year":"2016","unstructured":"Michellys P-Y, Chen B, Jiang T, Jin Y, Lu W, Marsilje TH, Pei W, Uno T, Zhu X, Wu B, Nguyen TN, Bursulaya B, Lee C, Li N, Kim S, Tuntland T, Liu B, Sun F, Steffy A, Hood T (2016) Design and synthesis of novel selective anaplastic lymphoma kinase inhibitors. Bioorg Med Chem Lett 26(3):1090\u20131096","journal-title":"Bioorg Med Chem Lett"},{"issue":"44","key":"355_CR15","doi-asserted-by":"crossref","first-page":"37447","DOI":"10.1074\/jbc.M112.391425","volume":"287","author":"LF Epstein","year":"2012","unstructured":"Epstein LF, Chen H, Emkey R, Whittington DA (2012) The R1275Q neuroblastoma mutant and certain ATP-competitive inhibitors stabilize alternative activation loop conformations of anaplastic lymphoma kinase. J Biol Chem 287(44):37447\u201337457","journal-title":"J Biol Chem"},{"issue":"8","key":"355_CR16","doi-asserted-by":"crossref","first-page":"3906","DOI":"10.1021\/acs.jmedchem.6b00106","volume":"59","author":"C-H Tu","year":"2016","unstructured":"Tu C-H, Lin W-H, Peng Y-H, Hsu T, Wu J-S, Chang C-Y, Lu C-T, Lyu P-C, Shih C, Jiaang W-T, Wu S-Y (2016) Pyrazolylamine derivatives reveal the conformational switching between type I and type ii binding modes of anaplastic lymphoma kinase (ALK). J Med Chem 59(8):3906\u20133919","journal-title":"J Med Chem"},{"issue":"10","key":"355_CR17","doi-asserted-by":"crossref","first-page":"4948","DOI":"10.1021\/acs.jmedchem.6b00306","volume":"59","author":"W-S Huang","year":"2016","unstructured":"Huang W-S, Liu S, Zou D, Thomas M, Wang Y, Zhou T, Romero J, Kohlmann A, Li F, Qi J, Cai L, Dwight TA, Xu Y, Xu R, Dodd R, Toms A, Parillon L, Lu X, Anjum R, Zhang S, Wang F, Keats J, Wardwell SD, Ning Y, Xu Q, Moran LE, Mohemmad QK, Jang HG, Clackson T, Narasimhan NI, Rivera VM, Zhu X, Dalgarno D, Shakespeare WC (2016) Discovery of Brigatinib (AP26113), a phosphine oxide-containing, potent, orally active inhibitor of anaplastic lymphoma kinase. J Med Chem 59(10):4948\u20134964","journal-title":"J Med Chem"},{"issue":"8","key":"355_CR18","doi-asserted-by":"crossref","first-page":"1910","DOI":"10.1016\/j.bmcl.2016.03.017","volume":"26","author":"P Zhang","year":"2016","unstructured":"Zhang P, Dong J, Zhong B, Zhang D, Yuan H, Jin C, Xu X, Li H, Zhou Y, Liang Z, Ji M, Xu T, Song G, Zhang L, Chen G, Meng X, Sun D, Shih J, Zhang R, Hou G, Wang C, Jin Y, Yang Q (2016) Design and synthesis of novel 3-sulfonylpyrazol-4-amino pyrimidines as potent anaplastic lymphoma kinase (ALK) inhibitors. Bioorg Med Chem Lett 26(8):1910\u20131918","journal-title":"Bioorg Med Chem Lett"},{"issue":"3","key":"355_CR19","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1042\/BJ20100609","volume":"430","author":"C Lee Christian","year":"2010","unstructured":"Lee Christian C, Jia Y, Li N, Sun X, Ng K, Ambing E, Gao M-Y, Hua S, Chen C, Kim S, Michellys P-Y, Lesley Scott A, Harris Jennifer L, Spraggon G (2010) Crystal structure of the ALK (anaplastic lymphoma kinase) catalytic domain. Biochem J 430(3):425\u2013437","journal-title":"Biochem J"},{"issue":"4","key":"355_CR20","doi-asserted-by":"crossref","first-page":"1698","DOI":"10.1021\/jm201565s","volume":"55","author":"MC Bryan","year":"2012","unstructured":"Bryan MC, Whittington DA, Doherty EM, Falsey JR, Cheng AC, Emkey R, Brake RL, Lewis RT (2012) Rapid development of piperidine carboxamides as potent and selective anaplastic lymphoma kinase inhibitors. J Med Chem 55(4):1698\u20131705","journal-title":"J Med Chem"},{"issue":"9","key":"355_CR21","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1021\/acsmedchemlett.8b00348","volume":"9","author":"TW Johnson","year":"2018","unstructured":"Johnson TW, Bolanos B, Brooun A, Gallego RA, Gehlhaar D, Jalaie M, McTigue M, Timofeevski S (2018) Reviving B-factors: activating ALK mutations increase protein dynamics of the unphosphorylated kinase. ACS Med Chem Lett 9(9):872\u2013877","journal-title":"ACS Med Chem Lett"},{"issue":"17","key":"355_CR22","doi-asserted-by":"crossref","first-page":"4911","DOI":"10.1016\/j.bmcl.2013.06.071","volume":"23","author":"VR Gummadi","year":"2013","unstructured":"Gummadi VR, Rajagopalan S, Looi C-Y, Paydar M, Renukappa GA, Ainan BR, Krishnamurthy NR, Panigrahi SK, Mahasweta K, Raghuramachandran S, Rajappa M, Ramanathan A, Lakshminarasimhan A, Ramachandra M, Wong P-F, Mustafa MR, Nanduri S, Hosahalli S (2013) Discovery of 7-azaindole based anaplastic lymphoma kinase (ALK) inhibitors: Wild type and mutant (L1196M) active compounds with unique binding mode. Bioorg Med Chem Lett 23(17):4911\u20134918","journal-title":"Bioorg Med Chem Lett"},{"issue":"18","key":"355_CR23","doi-asserted-by":"crossref","first-page":"6342","DOI":"10.1021\/jm2007613","volume":"54","author":"JJ Cui","year":"2011","unstructured":"Cui JJ, Tran-Dub\u00e9 M, Shen H, Nambu M, Kung P-P, Pairish M, Jia L, Meng J, Funk L, Botrous I, McTigue M, Grodsky N, Ryan K, Padrique E, Alton G, Timofeevski S, Yamazaki S, Li Q, Zou H, Christensen J, Mroczkowski B, Bender S, Kania RS, Edwards MP (2011) Structure based drug design of crizotinib (PF-02341066), a potent and selective dual inhibitor of mesenchymal-epithelial transition factor (c-MET) kinase and anaplastic lymphoma kinase (ALK). J Med Chem 54(18):6342\u20136363","journal-title":"J Med Chem"},{"issue":"14","key":"355_CR24","doi-asserted-by":"crossref","first-page":"5675","DOI":"10.1021\/jm400402q","volume":"56","author":"TH Marsilje","year":"2013","unstructured":"Marsilje TH, Pei W, Chen B, Lu W, Uno T, Jin Y, Jiang T, Kim S, Li N, Warmuth M, Sarkisova Y, Sun F, Steffy A, Pferdekamper AC, Li AG, Joseph SB, Kim Y, Liu B, Tuntland T, Cui X, Gray NS, Steensma R, Wan Y, Jiang J, Chopiuk G, Li J, Gordon WP, Richmond W, Johnson K, Chang J, Groessl T, He Y-Q, Phimister A, Aycinena A, Lee CC, Bursulaya B, Karanewsky DS, Seidel HM, Harris JL, Michellys P-Y (2013) Synthesis, structure-activity relationships, and in vivo efficacy of the novel potent and selective anaplastic lymphoma kinase (ALK) inhibitor 5-chloro-N2-(2-isopropoxy-5-methyl-4-(piperidin-4-yl)phenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine (LDK378) currently in Phase 1 and Phase 2 Clinical Trials. J Med Chem 56(14):5675\u20135690","journal-title":"J Med Chem"},{"key":"355_CR25","doi-asserted-by":"crossref","unstructured":"Kim D-W, Tiseo M, Ahn MJ, Reckamp KL, Hansen KH, Kim SW, Huber RM, West HL, Groen HJM, Hochmair MJ, Leighl NB, Gettinger SN, Langer CJ, Rodr\u00edguez LGPA, Smit EF, Kim ES, Reichmann W, Haluska FG, Kerstein D, Camidge DR (2017) Brigatinib in patients with crizotinib-refractory anaplastic lymphoma kinase-positive non-small-cell lung cancer: a randomized, multicenter phase II trial. J Clin Oncol.","DOI":"10.1200\/JCO.2016.71.5904"},{"issue":"1","key":"355_CR26","doi-asserted-by":"crossref","first-page":"14768","DOI":"10.1038\/ncomms14768","volume":"8","author":"K Uchibori","year":"2017","unstructured":"Uchibori K, Inase N, Araki M, Kamada M, Sato S, Okuno Y, Fujita N, Katayama R (2017) Brigatinib combined with anti-EGFR antibody overcomes osimertinib resistance in EGFR-mutated non-small-cell lung cancer. Nat Commun 8(1):14768","journal-title":"Nat Commun"},{"issue":"2","key":"355_CR27","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/S1470-2045(15)00488-X","volume":"17","author":"AT Shaw","year":"2016","unstructured":"Shaw AT, Gandhi L, Gadgeel S, Riely GJ, Cetnar J, West H, Camidge DR, Socinski MA, Chiappori A, Mekhail T, Chao BH, Borghaei H, Gold KA, Zeaiter A, Bordogna W, Balas B, Puig O, Henschel V, Ou S-HI (2016) Alectinib in ALK-positive, crizotinib-resistant, non-small-cell lung cancer: a single-group, multicentre, phase 2 trial. Lancet Oncol 17(2):234\u2013242","journal-title":"Lancet Oncol"},{"issue":"2","key":"355_CR28","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1158\/1535-7163.MCT-13-0395","volume":"13","author":"M Mori","year":"2014","unstructured":"Mori M, Ueno Y, Konagai S, Fushiki H, Shimada I, Kondoh Y, Saito R, Mori K, Shindou N, Soga T, Sakagami H, Furutani T, Doihara H, Kudoh M, Kuromitsu S (2014) The selective anaplastic lymphoma receptor tyrosine kinase inhibitor ASP3026 induces tumor regression and prolongs survival in non-small cell lung cancer model mice. Mol Cancer Ther 13(2):329\u2013340","journal-title":"Mol Cancer Ther"},{"issue":"6","key":"355_CR29","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1038\/nrc3526","volume":"13","author":"N-KV Cheung","year":"2013","unstructured":"Cheung N-KV, Dyer MA (2013) Neuroblastoma: developmental biology, cancer genomics and immunotherapy. Nat Rev Cancer 13(6):397\u2013411","journal-title":"Nat Rev Cancer"},{"issue":"4","key":"355_CR30","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1021\/jm401805h","volume":"57","author":"Q Huang","year":"2014","unstructured":"Huang Q, Johnson TW, Bailey S, Brooun A, Bunker KD, Burke BJ, Collins MR, Cook AS, Cui JJ, Dack KN, Deal JG, Deng Y-L, Dinh D, Engstrom LD, He M, Hoffman J, Hoffman RL, Johnson PS, Kania RS, Lam H, Lam JL, Le PT, Li Q, Lingardo L, Liu W, Lu MW, McTigue M, Palmer CL, Richardson PF, Sach NW, Shen H, Smeal T, Smith GL, Stewart AE, Timofeevski S, Tsaparikos K, Wang H, Zhu H, Zhu J, Zou HY, Edwards MP (2014) Design of potent and selective inhibitors to overcome clinical anaplastic lymphoma kinase mutations resistant to crizotinib. J Med Chem 57(4):1170\u20131187","journal-title":"J Med Chem"},{"issue":"10","key":"355_CR31","doi-asserted-by":"crossref","first-page":"3462","DOI":"10.1002\/jcb.26004","volume":"118","author":"N Nagasundaram","year":"2017","unstructured":"Nagasundaram N, Wilson Alphonse CR, Samuel Gnana PV, Rajaretinam RK (2017) Molecular dynamics validation of crizotinib resistance to ALK mutations (L1196M and G1269A) and identification of specific inhibitors. J Cell Biochem 118(10):3462\u20133471","journal-title":"J Cell Biochem"},{"issue":"1","key":"355_CR32","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1056\/NEJMoa1508887","volume":"374","author":"AT Shaw","year":"2015","unstructured":"Shaw AT, Friboulet L, Leshchiner I, Gainor JF, Bergqvist S, Brooun A, Burke BJ, Deng Y-L, Liu W, Dardaei L, Frias RL, Schultz KR, Logan J, James LP, Smeal T, Timofeevski S, Katayama R, Iafrate AJ, Le L, McTigue M, Getz G, Johnson TW, Engelman JA (2015) Resensitization to crizotinib by the Lorlatinib ALK resistance mutation L1198F. New Engl J Med 374(1):54\u201361","journal-title":"New Engl J Med"},{"issue":"7215","key":"355_CR33","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1038\/nature07398","volume":"455","author":"I Janoueix-Lerosey","year":"2008","unstructured":"Janoueix-Lerosey I, Lequin D, Brugi\u00e8res L, Ribeiro A, de Pontual L, Combaret V, Raynal V, Puisieux A, Schleiermacher G, Pierron G, Valteau-Couanet D, Frebourg T, Michon J, Lyonnet S, Amiel J, Delattre O (2008) Somatic and germline activating mutations of the ALK kinase receptor in neuroblastoma. Nature 455(7215):967\u2013970","journal-title":"Nature"},{"issue":"5","key":"355_CR34","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1016\/j.ccell.2014.09.019","volume":"26","author":"C Bresler Scott","year":"2014","unstructured":"Bresler Scott C, Weiser Daniel A, Huwe Peter J, Park Jin H, Krytska K, Ryles H, Laudenslager M, Rappaport Eric F, Wood Andrew C, McGrady Patrick W, Hogarty Michael D, London Wendy B, Radhakrishnan R, Lemmon Mark A, Moss\u00e9 Ya\u00ebl P (2014) ALK mutations confer differential oncogenic activation and sensitivity to ALK inhibition therapy in neuroblastoma. Cancer Cell 26(5):682\u2013694","journal-title":"Cancer Cell"},{"issue":"7215","key":"355_CR35","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1038\/nature07261","volume":"455","author":"YP Moss\u00e9","year":"2008","unstructured":"Moss\u00e9 YP, Laudenslager M, Longo L, Cole KA, Wood A, Attiyeh EF, Laquaglia MJ, Sennett R, Lynch JE, Perri P, Laureys G, Speleman F, Kim C, Hou C, Hakonarson H, Torkamani A, Schork NJ, Brodeur GM, Tonini GP, Rappaport E, Devoto M, Maris JM (2008) Identification of ALK as a major familial neuroblastoma predisposition gene. Nature 455(7215):930\u2013935","journal-title":"Nature"},{"issue":"10","key":"355_CR36","doi-asserted-by":"crossref","first-page":"4915","DOI":"10.1021\/acs.jmedchem.8b01630","volume":"62","author":"M Fushimi","year":"2019","unstructured":"Fushimi M, Fujimori I, Wakabayashi T, Hasui T, Kawakita Y, Imamura K, Kato T, Murakami M, Ishii T, Kikko Y, Kasahara M, Nakatani A, Hiura Y, Miyamoto M, Saikatendu K, Zou H, Lane SW, Lawson JD, Imoto H (2019) Discovery of potent, selective, and brain-penetrant 1H-Pyrazol-5-yl-1H-pyrrolo[2,3-b]pyridines as anaplastic lymphoma kinase (ALK) inhibitors. J Med Chem 62(10):4915\u20134935","journal-title":"J Med Chem"},{"issue":"5","key":"355_CR37","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1021\/acschemneuro.7b00490","volume":"9","author":"W Xue","year":"2018","unstructured":"Xue W, Yang F, Wang P, Zheng G, Chen Y, Yao X, Zhu F (2018) What contributes to serotonin-norepinephrine reuptake inhibitors\u2019 dual-targeting mechanism? The key role of transmembrane domain 6 in human serotonin and norepinephrine transporters revealed by molecular dynamics simulation. ACS Chem Neurosci 9(5):1128\u20131140","journal-title":"ACS Chem Neurosci"},{"issue":"6","key":"355_CR38","doi-asserted-by":"crossref","first-page":"1492","DOI":"10.1021\/acschemneuro.8b00059","volume":"9","author":"T Fu","year":"2018","unstructured":"Fu T, Zheng G, Tu G, Yang F, Chen Y, Yao X, Li X, Xue W, Zhu F (2018) Exploring the binding mechanism of metabotropic glutamate receptor 5 negative allosteric modulators in clinical trials by molecular dynamics simulations. ACS Chem Neurosci 9(6):1492\u20131502","journal-title":"ACS Chem Neurosci"},{"issue":"1","key":"355_CR39","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.jsb.2010.07.013","volume":"173","author":"M-J Yang","year":"2011","unstructured":"Yang M-J, Pang X-Q, Zhang X, Han K-L (2011) Molecular dynamics simulation reveals preorganization of the chloroplast FtsY towards complex formation induced by GTP binding. J Struct Biol 173(1):57\u201366","journal-title":"J Struct Biol"},{"issue":"19","key":"355_CR40","doi-asserted-by":"crossref","first-page":"5815","DOI":"10.1021\/acs.jpclett.9b02209","volume":"10","author":"Y Xu","year":"2019","unstructured":"Xu Y, Li S, Yan Z, Ge B, Huang F, Yue T (2019) Revealing cooperation between knotted conformation and dimerization in protein stabilization by molecular dynamics simulations. J Phys Chem Lett 10(19):5815\u20135822","journal-title":"J Phys Chem Lett"},{"issue":"40","key":"355_CR41","doi-asserted-by":"crossref","first-page":"15884","DOI":"10.1021\/jacs.9b06977","volume":"141","author":"S Zhang","year":"2019","unstructured":"Zhang S, Lin X (2019) Lipid acyl chain cis double bond position modulates membrane domain registration\/anti-registration. J Am Chem Soc 141(40):15884\u201315890","journal-title":"J Am Chem Soc"},{"issue":"11","key":"355_CR42","doi-asserted-by":"crossref","first-page":"3524","DOI":"10.3390\/ijms19113524","volume":"19","author":"G Hu","year":"2018","unstructured":"Hu G, Yu X, Bian Y, Cao Z, Xu S, Zhao L, Ji B, Wang W, Wang J (2018) Atomistic analysis of ToxN and ToxI complex unbinding mechanism. Int J Mol Sci 19(11):3524","journal-title":"Int J Mol Sci"},{"issue":"8","key":"355_CR43","doi-asserted-by":"crossref","first-page":"4464","DOI":"10.1039\/C9CP06657H","volume":"22","author":"R-G Wang","year":"2020","unstructured":"Wang R-G, Zhang H-X, Zheng Q-C (2020) Revealing the binding and drug resistance mechanism of amprenavir, indinavir, ritonavir, and nelfinavir complexed with HIV-1 protease due to double mutations G48T\/L89M by molecular dynamics simulations and free energy analyses. Phys Chem Chem Phys 22(8):4464\u20134480","journal-title":"Phys Chem Chem Phys"},{"key":"355_CR44","doi-asserted-by":"crossref","unstructured":"Wu EL, Han K, Zhang JZH (2008) Selectivity of neutral\/weakly basic P1 group inhibitors of thrombin and trypsin by a molecular dynamics study. Chem Eur J 14(28): 8704\u20138714","DOI":"10.1002\/chem.200800277"},{"issue":"13","key":"355_CR45","doi-asserted-by":"crossref","first-page":"6618","DOI":"10.1093\/nar\/gkz499","volume":"47","author":"J Chen","year":"2019","unstructured":"Chen J, Wang X, Pang L, Zhang JZH, Zhu T (2019) Effect of mutations on binding of ligands to guanine riboswitch probed by free energy perturbation and molecular dynamics simulations. Nucleic Acids Res 47(13):6618\u20136631","journal-title":"Nucleic Acids Res"},{"issue":"17","key":"355_CR46","doi-asserted-by":"crossref","first-page":"5722","DOI":"10.1021\/jacs.6b02682","volume":"138","author":"L Duan","year":"2016","unstructured":"Duan L, Liu X, Zhang JZH (2016) Interaction entropy: a new paradigm for highly efficient and reliable computation of protein-ligand binding free energy. J Am Chem Soc 138(17):5722\u20135728","journal-title":"J Am Chem Soc"},{"issue":"5","key":"355_CR47","doi-asserted-by":"crossref","first-page":"2467","DOI":"10.1021\/acschemneuro.8b00729","volume":"10","author":"Y Zhang","year":"2019","unstructured":"Zhang Y, Ying JB, Hong JJ, Li FC, Fu TT, Yang FY, Zheng GX, Yao XJ, Lou Y, Qiu Y, Xue WW, Zhu F (2019) How does chirality determine the selective inhibition of histone deacetylase 6? A lesson from trichostatin A enantiomers based on molecular dynamics. ACS Chem Neurosci 10(5):2467\u20132480","journal-title":"ACS Chem Neurosci"},{"issue":"16","key":"355_CR48","doi-asserted-by":"crossref","first-page":"8870","DOI":"10.1039\/D0CP00763C","volume":"22","author":"B Lin","year":"2020","unstructured":"Lin B, Zhang H, Zheng Q (2020) How do mutations affect the structural characteristics and substrate binding of CYP21A2? An investigation by molecular dynamics simulations. Phys Chem Chem Phys 22(16):8870\u20138877","journal-title":"Phys Chem Chem Phys"},{"issue":"9","key":"355_CR49","doi-asserted-by":"crossref","first-page":"6606","DOI":"10.1039\/C7CP07869B","volume":"20","author":"W Xue","year":"2018","unstructured":"Xue W, Wang P, Tu G, Yang F, Zheng G, Li X, Li X, Chen Y, Yao X, Zhu F (2018) Computational identification of the binding mechanism of a triple reuptake inhibitor amitifadine for the treatment of major depressive disorder. Phys Chem Chem Phys 20(9):6606\u20136616","journal-title":"Phys Chem Chem Phys"},{"issue":"5","key":"355_CR50","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1007\/s10822-020-00294-1","volume":"34","author":"Z Sun","year":"2020","unstructured":"Sun Z, He Q, Li X, Zhu Z (2020) SAMPL6 host\u2013guest binding affinities and binding poses from spherical-coordinates-biased simulations. J Comput Aid Mol Des 34(5):589\u2013600","journal-title":"J Comput Aid Mol Des"},{"issue":"4","key":"355_CR51","doi-asserted-by":"crossref","first-page":"2262","DOI":"10.1039\/C9CP05704H","volume":"22","author":"J Chen","year":"2020","unstructured":"Chen J, Liu X, Zhang S, Chen J, Sun H, Zhang L, Zhang Q (2020) Molecular mechanism with regard to the binding selectivity of inhibitors toward FABP5 and FABP7 explored by multiple short molecular dynamics simulations and free energy analyses. Phys Chem Chem Phys 22(4):2262\u20132275","journal-title":"Phys Chem Chem Phys"},{"issue":"2","key":"355_CR52","doi-asserted-by":"crossref","first-page":"e23257","DOI":"10.1002\/bip.23257","volume":"110","author":"M-Y He","year":"2019","unstructured":"He M-Y, Li W-K, Meiler J, Zheng Q-C, Zhang H-X (2019) Insight on mutation-induced resistance to anaplastic lymphoma kinase inhibitor ceritinib from molecular dynamics simulations. Biopolymers 110(2):e23257","journal-title":"Biopolymers"},{"issue":"1","key":"355_CR53","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1002\/jcb.27412","volume":"120","author":"J Tu","year":"2019","unstructured":"Tu J, Song LT, Liu RR, Zhai HL, Wang J, Zhang XY (2019) Molecular inhibitory mechanism study on the potent inhibitor brigatinib against four crizotinib-resistant ALK mutations. J Cell Biochem 120(1):562\u2013574","journal-title":"J Cell Biochem"},{"issue":"24","key":"355_CR54","doi-asserted-by":"crossref","first-page":"10927","DOI":"10.1021\/acs.jmedchem.9b00446","volume":"62","author":"X Kong","year":"2019","unstructured":"Kong X, Pan P, Sun H, Xia H, Wang X, Li Y, Hou T (2019) Drug discovery targeting anaplastic lymphoma kinase (ALK). J Med Chem 62(24):10927\u201310954","journal-title":"J Med Chem"},{"issue":"11","key":"355_CR55","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1021\/acscentsci.7b00419","volume":"3","author":"P Pan","year":"2017","unstructured":"Pan P, Yu H, Liu Q, Kong X, Chen H, Chen J, Liu Q, Li D, Kang Y, Sun H, Zhou W, Tian S, Cui S, Zhu F, Li Y, Huang Y, Hou T (2017) Combating drug-resistant mutants of anaplastic lymphoma kinase with potent and selective type-I1\/2 inhibitors by stabilizing unique DFG-shifted loop conformation. ACS Central Sci 3(11):1208\u20131220","journal-title":"ACS Central Sci"},{"issue":"44","key":"355_CR56","doi-asserted-by":"crossref","first-page":"30239","DOI":"10.1039\/C7CP05418A","volume":"19","author":"J Chen","year":"2017","unstructured":"Chen J, Wang J, Zhu W (2017) Mutation L1196M-induced conformational changes and the drug resistant mechanism of anaplastic lymphoma kinase studied by free energy perturbation and umbrella sampling. Phys Chem Chem Phys 19(44):30239\u201330248","journal-title":"Phys Chem Chem Phys"},{"issue":"7","key":"355_CR57","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.1021\/acschemneuro.8b00105","volume":"9","author":"M-Y He","year":"2018","unstructured":"He M-Y, Li W-K, Zheng Q-C, Zhang H-X (2018) Conformational transition of key structural features involved in activation of ALK induced by two neuroblastoma mutations and ATP binding: insight from accelerated molecular dynamics simulations. ACS Chem Neurosci 9(7):1783\u20131792","journal-title":"ACS Chem Neurosci"},{"issue":"37","key":"355_CR58","doi-asserted-by":"crossref","first-page":"20951","DOI":"10.1039\/C9CP02851J","volume":"21","author":"Z Xiao","year":"2019","unstructured":"Xiao Z, Cong Y, Huang K, Zhong S, Zhang JZH, Duan L (2019) Drug-resistance mechanisms of three mutations in anaplastic lymphoma kinase against two inhibitors based on MM\/PBSA combined with interaction entropy. Phys Chem Chem Phys 21(37):20951\u201320964","journal-title":"Phys Chem Chem Phys"},{"issue":"8","key":"355_CR59","doi-asserted-by":"crossref","first-page":"3584","DOI":"10.1021\/acs.jctc.5b00436","volume":"11","author":"Y Miao","year":"2015","unstructured":"Miao Y, Feher VA, McCammon JA (2015) Gaussian accelerated molecular dynamics: unconstrained enhanced sampling and free energy calculation. J Chem Theory Comput 11(8):3584\u20133595","journal-title":"J Chem Theory Comput"},{"issue":"43","key":"355_CR60","doi-asserted-by":"crossref","first-page":"12162","DOI":"10.1073\/pnas.1614538113","volume":"113","author":"Y Miao","year":"2016","unstructured":"Miao Y, McCammon JA (2016) Graded activation and free energy landscapes of a muscarinic G-protein\u2013coupled receptor. Proc Natl Acad Sci U S A 113(43):12162\u201312167","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"30","key":"355_CR61","doi-asserted-by":"crossref","first-page":"6462","DOI":"10.1021\/acs.jpcb.9b04867","volume":"123","author":"J Wang","year":"2019","unstructured":"Wang J, Miao Y (2019) Mechanistic insights into specific G protein interactions with adenosine receptors. J Phys Chem B 123(30):6462\u20136473","journal-title":"J Phys Chem B"},{"issue":"112","key":"355_CR62","doi-asserted-by":"crossref","first-page":"112","DOI":"10.3389\/fmolb.2019.00112","volume":"6","author":"J Wang","year":"2019","unstructured":"Wang J, Alekseenko A, Kozakov D, Miao Y (2019) Improved modeling of peptide-protein binding through global docking and accelerated molecular dynamics simulations. Front Mol Biosci 6(112):112","journal-title":"Front Mol Biosci"},{"issue":"4","key":"355_CR63","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1021\/acscentsci.9b00020","volume":"5","author":"CG Ricci","year":"2019","unstructured":"Ricci CG, Chen JS, Miao Y, Jinek M, Doudna JA, McCammon JA, Palermo G (2019) Deciphering off-target effects in CRISPR-Cas9 through accelerated molecular dynamics. ACS Central Sci 5(4):651\u2013662","journal-title":"ACS Central Sci"},{"issue":"4","key":"355_CR64","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1021\/acschemneuro.9b00630","volume":"11","author":"X An","year":"2020","unstructured":"An X, Bai Q, Bing Z, Liu H, Zhang Q, Liu H, Yao X (2020) Revealing the positive binding cooperativity mechanism between the orthosteric and the allosteric antagonists of CCR2 by metadynamics and Gaussian accelerated molecular dynamics simulations. ACS Chem Neurosci 11(4):628\u2013637","journal-title":"ACS Chem Neurosci"},{"key":"355_CR65","doi-asserted-by":"crossref","first-page":"540","DOI":"10.3389\/fchem.2019.00540","volume":"7","author":"L Duan","year":"2019","unstructured":"Duan L, Gue X, Cong Y, Feng G, Li Y, Zhang JZH (2019) Accelerated molecular dynamics simulation for helical proteins folding in explicit water. Front Chem 7:540","journal-title":"Front Chem"},{"issue":"37","key":"355_CR66","doi-asserted-by":"crossref","first-page":"21238","DOI":"10.1039\/D0CP03766D","volume":"22","author":"J Chen","year":"2020","unstructured":"Chen J, Wang W, Pang L, Zhu W (2020) Unveiling conformational dynamics changes of H-Ras induced by mutations based on accelerated molecular dynamics. Phys Chem Chem Phys 22(37):21238\u201321250","journal-title":"Phys Chem Chem Phys"},{"issue":"2","key":"355_CR67","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1002\/prot.340230207","volume":"23","author":"S Hayward","year":"1995","unstructured":"Hayward S, Kitao A, G\u014d N (1995) Harmonicity and anharmonicity in protein dynamics: a normal mode analysis and principal component analysis. Proteins Struct Funct Genet 23(2):177\u2013186","journal-title":"Proteins Struct Funct Genet"},{"key":"355_CR68","doi-asserted-by":"crossref","unstructured":"Amadei A, Linssen ABM, Berendsen HJC (1993) Essential dynamics of proteins. Proteins Struct Funct Genet 17(4): 412\u2013425.","DOI":"10.1002\/prot.340170408"},{"issue":"3","key":"355_CR69","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1002\/prot.340110305","volume":"11","author":"T Ichiye","year":"1991","unstructured":"Ichiye T, Karplus M (1991) Collective motions in proteins: a covariance analysis of atomic fluctuations in molecular dynamics and normal mode simulations. Proteins Struct Funct Genet 11(3):205\u2013217","journal-title":"Proteins Struct Funct Genet"},{"issue":"6","key":"355_CR70","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1002\/bip.360230610","volume":"23","author":"RM Levy","year":"1984","unstructured":"Levy RM, Srinivasan AR, Olson WK, McCammon JA (1984) Quasi-harmonic method for studying very low frequency modes in proteins. Biopolymers 23(6):1099\u20131112","journal-title":"Biopolymers"},{"key":"355_CR71","doi-asserted-by":"crossref","unstructured":"Webb B, Sali A (2014) Comparative protein structure modeling using MODELLER. Current protocols in bioinformatics. Wiley, pp 2015.2016.2011\u20132015.2016.2032.","DOI":"10.1002\/0471250953.bi0506s47"},{"issue":"4","key":"355_CR72","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1002\/prot.20660","volume":"61","author":"H Li","year":"2005","unstructured":"Li H, Robertson AD, Jensen JH (2005) Very fast empirical prediction and rationalization of protein pKa values. Proteins Struct Funct Genet 61(4):704\u2013721","journal-title":"Proteins Struct Funct Genet"},{"issue":"3","key":"355_CR73","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1002\/prot.22102","volume":"73","author":"DC Bas","year":"2008","unstructured":"Bas DC, Rogers DM, Jensen JH (2008) Very fast prediction and rationalization of pKa values for protein\u2013ligand complexes. Proteins Struct Funct Genet 73(3):765\u2013783","journal-title":"Proteins Struct Funct Genet"},{"issue":"16","key":"355_CR74","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1002\/jcc.10128","volume":"23","author":"A Jakalian","year":"2002","unstructured":"Jakalian A, Jack DB, Bayly CI (2002) Fast, efficient generation of high-quality atomic charges. AM1-BCC model: II. Parameterization and validation. J Comput Chem 23(16):1623\u20131641","journal-title":"J Comput Chem"},{"issue":"2","key":"355_CR75","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1002\/(SICI)1096-987X(20000130)21:2<132::AID-JCC5>3.0.CO;2-P","volume":"21","author":"A Jakalian","year":"2000","unstructured":"Jakalian A, Bush BL, Jack DB, Bayly CI (2000) Fast, efficient generation of high-quality atomic charges. AM1-BCC model: I. Method. J Comput Chem 21(2):132\u2013146","journal-title":"J Comput Chem"},{"issue":"2","key":"355_CR76","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1002\/wcms.1121","volume":"3","author":"R Salomon-Ferrer","year":"2013","unstructured":"Salomon-Ferrer R, Case DA, Walker RC (2013) An overview of the Amber biomolecular simulation package. WIREs Comput Mol Sci 3(2):198\u2013210","journal-title":"WIREs Comput Mol Sci"},{"issue":"16","key":"355_CR77","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1002\/jcc.20290","volume":"26","author":"DA Case","year":"2005","unstructured":"Case DA, Cheatham TE III, Darden T, Gohlke H, Luo R, Merz KM Jr, Onufriev A, Simmerling C, Wang B, Woods RJ (2005) The Amber biomolecular simulation programs. J Comput Chem 26(16):1668\u20131688","journal-title":"J Comput Chem"},{"issue":"8","key":"355_CR78","doi-asserted-by":"crossref","first-page":"3696","DOI":"10.1021\/acs.jctc.5b00255","volume":"11","author":"JA Maier","year":"2015","unstructured":"Maier JA, Martinez C, Kasavajhala K, Wickstrom L, Hauser KE, Simmerling C (2015) ff14SB: improving the accuracy of protein side chain and backbone parameters from ff99SB. J Chem Theory Comput 11(8):3696\u20133713","journal-title":"J Chem Theory Comput"},{"issue":"5","key":"355_CR79","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1021\/acs.jcim.7b00135","volume":"57","author":"D Song","year":"2017","unstructured":"Song D, Luo R, Chen H-F (2017) The IDP-specific force field ff14IDPSFF improves the conformer sampling of intrinsically disordered proteins. J Chem Inf Model 57(5):1166\u20131178","journal-title":"J Chem Inf Model"},{"issue":"9","key":"355_CR80","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1002\/jcc.20035","volume":"25","author":"J Wang","year":"2004","unstructured":"Wang J, Wolf RM, Caldwell JW, Kollman PA, Case DA (2004) Development and testing of a general amber force field. J Comput Chem 25(9):1157\u20131174","journal-title":"J Comput Chem"},{"issue":"2","key":"355_CR81","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1063\/1.445869","volume":"79","author":"WL Jorgensen","year":"1983","unstructured":"Jorgensen WL, Chandrasekhar J, Madura JD, Impey RW, Klein ML (1983) Comparison of simple potential functions for simulating liquid water. J Chem Phys 79(2):926\u2013935","journal-title":"J Chem Phys"},{"issue":"21","key":"355_CR82","doi-asserted-by":"crossref","first-page":"8021","DOI":"10.1021\/j100384a009","volume":"94","author":"J \u0226qvist","year":"1990","unstructured":"\u0226qvist J (1990) Ion-water interaction potentials derived from free energy perturbation simulations. J Phys Chem B 94(21):8021\u20138024","journal-title":"J Phys Chem B"},{"issue":"12","key":"355_CR83","doi-asserted-by":"crossref","first-page":"10089","DOI":"10.1063\/1.464397","volume":"98","author":"T Darden","year":"1993","unstructured":"Darden T, York D, Pedersen L (1993) Particle mesh Ewald: an N\u22c5log(N) method for Ewald sums in large systems. J Chem Phys 98(12):10089\u201310092","journal-title":"J Chem Phys"},{"issue":"19","key":"355_CR84","doi-asserted-by":"crossref","first-page":"8577","DOI":"10.1063\/1.470117","volume":"103","author":"U Essmann","year":"1995","unstructured":"Essmann U, Perera L, Berkowitz ML, Darden T, Lee H, Pedersen LG (1995) A smooth particle mesh Ewald method. J Chem Phys 103(19):8577\u20138593","journal-title":"J Chem Phys"},{"issue":"7","key":"355_CR85","doi-asserted-by":"crossref","first-page":"2677","DOI":"10.1021\/ct500090q","volume":"10","author":"Y Miao","year":"2014","unstructured":"Miao Y, Sinko W, Pierce L, Bucher D, Walker RC, McCammon JA (2014) Improved reweighting of accelerated molecular dynamics simulations for free energy calculation. J Chem Theory Comput 10(7):2677\u20132689","journal-title":"J Chem Theory Comput"},{"issue":"3","key":"355_CR86","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/0021-9991(77)90098-5","volume":"23","author":"J-P Ryckaert","year":"1977","unstructured":"Ryckaert J-P, Ciccotti G, Berendsen HJC (1977) Numerical integration of the cartesian equations of motion of a system with constraints: molecular dynamics of n-alkanes. J Comput Phys 23(3):327\u2013341","journal-title":"J Comput Phys"},{"issue":"5","key":"355_CR87","doi-asserted-by":"crossref","first-page":"2090","DOI":"10.1063\/1.1332996","volume":"114","author":"JA Izaguirre","year":"2001","unstructured":"Izaguirre JA, Catarello DP, Wozniak JM, Skeel RD (2001) Langevin stabilization of molecular dynamics. J Chem Phys 114(5):2090\u20132098","journal-title":"J Chem Phys"},{"issue":"2","key":"355_CR88","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/j.cpc.2012.09.022","volume":"184","author":"S Le Grand","year":"2013","unstructured":"Le Grand S, G\u00f6tz AW, Walker RC (2013) SPFP: speed without compromise\u2014a mixed precision model for GPU accelerated molecular dynamics simulations. Comput Phys Commun 184(2):374\u2013380","journal-title":"Comput Phys Commun"},{"issue":"9","key":"355_CR89","doi-asserted-by":"crossref","first-page":"3878","DOI":"10.1021\/ct400314y","volume":"9","author":"R Salomon-Ferrer","year":"2013","unstructured":"Salomon-Ferrer R, G\u00f6tz AW, Poole D, Le Grand S, Walker RC (2013) Routine microsecond molecular dynamics simulations with AMBER on GPUs. 2. Explicit solvent particle mesh Ewald. J Chem Theory Comput 9(9):3878\u20133888","journal-title":"J Chem Theory Comput"},{"issue":"5","key":"355_CR90","doi-asserted-by":"crossref","first-page":"1542","DOI":"10.1021\/ct200909j","volume":"8","author":"AW G\u00f6tz","year":"2012","unstructured":"G\u00f6tz AW, Williamson MJ, Xu D, Poole D, Le Grand S, Walker RC (2012) Routine microsecond molecular dynamics simulations with AMBER on GPUs. 1. Generalized Born. J Chem Theory Comput 8(5):1542\u20131555","journal-title":"J Chem Theory Comput"},{"issue":"7","key":"355_CR91","doi-asserted-by":"crossref","first-page":"3084","DOI":"10.1021\/ct400341p","volume":"9","author":"DR Roe","year":"2013","unstructured":"Roe DR, Cheatham TE (2013) PTRAJ and CPPTRAJ: software for processing and analysis of molecular dynamics trajectory data. J Chem Theory Comput 9(7):3084\u20133095","journal-title":"J Chem Theory Comput"},{"issue":"10","key":"355_CR92","doi-asserted-by":"crossref","first-page":"4303","DOI":"10.1021\/acschemneuro.9b00348","volume":"10","author":"J Chen","year":"2019","unstructured":"Chen J, Wang J, Yin B, Pang L, Wang W, Zhu W (2019) Molecular mechanism of binding selectivity of inhibitors toward BACE1 and BACE2 revealed by multiple short molecular dynamics simulations and free-energy predictions. ACS Chem Neurosci 10(10):4303\u20134318","journal-title":"ACS Chem Neurosci"},{"issue":"12","key":"355_CR93","doi-asserted-by":"crossref","first-page":"1811","DOI":"10.1021\/acschemneuro.0c00234","volume":"11","author":"J Chen","year":"2020","unstructured":"Chen J, Yin B, Wang W, Sun H (2020) Effects of disulfide bonds on binding of inhibitors to \u03b2-amyloid cleaving enzyme 1 decoded by multiple replica accelerated molecular dynamics simulations. ACS Chem Neurosci 11(12):1811\u20131826","journal-title":"ACS Chem Neurosci"},{"issue":"1","key":"355_CR94","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/0263-7855(96)00018-5","volume":"14","author":"W Humphrey","year":"1996","unstructured":"Humphrey W, Dalke A, Schulten K (1996) VMD: visual molecular dynamics. J Mol Graph 14(1):33\u201338","journal-title":"J Mol Graph"},{"issue":"4","key":"355_CR95","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1006\/jmbi.2000.4057","volume":"303","author":"W Wang","year":"2000","unstructured":"Wang W, Kollman PA (2000) Free energy calculations on dimer stability of the HIV protease using molecular dynamics and a continuum solvent model11Edited by B Honig. J Mol Biol 303(4):567\u2013582","journal-title":"J Mol Biol"},{"issue":"26","key":"355_CR96","doi-asserted-by":"crossref","first-page":"14937","DOI":"10.1073\/pnas.251265598","volume":"98","author":"W Wang","year":"2001","unstructured":"Wang W, Kollman PA (2001) Computational study of protein specificity: The molecular basis of HIV-1 protease drug resistance. Proc Natl Acad Sci USA 98(26):14937\u201314942","journal-title":"Proc Natl Acad Sci USA"},{"issue":"87","key":"355_CR97","doi-asserted-by":"crossref","first-page":"87","DOI":"10.3389\/fmolb.2017.00087","volume":"4","author":"C Wang","year":"2018","unstructured":"Wang C, Greene DA, Xiao L, Qi R, Luo R (2018) Recent developments and applications of the MMPBSA method. Front Mol Biosci 4(87):87","journal-title":"Front Mol Biosci"},{"key":"355_CR98","doi-asserted-by":"crossref","unstructured":"Hu G, Li H, Xu S, Wang J (2020) Ligand binding mechanism and its relationship with conformational changes in Adenine Riboswitch. Int J Mol Sci 21(6): 1926.","DOI":"10.3390\/ijms21061926"},{"key":"355_CR99","doi-asserted-by":"crossref","unstructured":"Hou T, Wang J, Li Y, Wang W (2011) Assessing the performance of the molecular mechanics\/Poisson Boltzmann surface area and molecular mechanics\/generalized Born surface area methods. II. The accuracy of ranking poses generated from docking. J Comput Chem 32(5): 866\u2013877.","DOI":"10.1002\/jcc.21666"},{"key":"355_CR100","doi-asserted-by":"crossref","unstructured":"Sun H, Li Y, Tian S, Xu L, Hou T (2014) Assessing the performance of MM\/PBSA and MM\/GBSA methods. 4. Accuracies of MM\/PBSA and MM\/GBSA methodologies evaluated by various simulation protocols using PDBbind data set. Phys Chem Chem Phys 16(31): 16719\u201316729.","DOI":"10.1039\/C4CP01388C"},{"key":"355_CR101","doi-asserted-by":"crossref","unstructured":"Sun H, Li Y, Shen M, Tian S, Xu L, Pan P, Guan Y, Hou T (2014) Assessing the performance of MM\/PBSA and MM\/GBSA methods. 5. Improved docking performance using high solute dielectric constant MM\/GBSA and MM\/PBSA rescoring. Phys Chem Chem Phys 16(40): 22035\u201322045.","DOI":"10.1039\/C4CP03179B"},{"issue":"9","key":"355_CR102","doi-asserted-by":"crossref","first-page":"3314","DOI":"10.1021\/ct300418h","volume":"8","author":"BR Miller","year":"2012","unstructured":"Miller BR, McGee TD, Swails JM, Homeyer N, Gohlke H, Roitberg AE (2012) MMPBSA.py: an efficient program for end-state free energy calculations. J Chem Theory Comput 8(9):3314\u20133321","journal-title":"J Chem Theory Comput"},{"issue":"2","key":"355_CR103","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1002\/prot.20033","volume":"55","author":"A Onufriev","year":"2004","unstructured":"Onufriev A, Bashford D, Case DA (2004) Exploring protein native states and large-scale conformational changes with a modified generalized born model. Proteins Struct Funct Genet 55(2):383\u2013394","journal-title":"Proteins Struct Funct Genet"},{"issue":"4","key":"355_CR104","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1016\/S0022-2836(03)00610-7","volume":"330","author":"H Gohlke","year":"2003","unstructured":"Gohlke H, Kiel C, Case DA (2003) Insights into protein-protein binding by binding free energy calculation and free energy decomposition for the Ras-Raf and Ras\u2013RalGDS complexes. J Mol Biol 330(4):891\u2013913","journal-title":"J Mol Biol"},{"issue":"9","key":"355_CR105","doi-asserted-by":"crossref","first-page":"1903","DOI":"10.1021\/acs.jcim.5b00173","volume":"55","author":"J Chen","year":"2015","unstructured":"Chen J, Wang X, Zhu T, Zhang Q, Zhang JZH (2015) A Comparative insight into amprenavir resistance of mutations V32I, G48V, I50V, I54V, and I84V in HIV-1 protease based on thermodynamic integration and MM-PBSA methods. J Chem Inf Model 55(9):1903\u20131913","journal-title":"J Chem Inf Model"},{"issue":"36","key":"355_CR106","doi-asserted-by":"crossref","first-page":"11396","DOI":"10.1021\/jp8015886","volume":"112","author":"Y Ding","year":"2008","unstructured":"Ding Y, Mei Y, Zhang JZH (2008) Quantum mechanical studies of residue-specific hydrophobic interactions in p53\u2212MDM2 binding. J Phys Chem B 112(36):11396\u201311401","journal-title":"J Phys Chem B"}],"container-title":["Journal of Computer-Aided Molecular Design"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10822-020-00355-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10822-020-00355-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10822-020-00355-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,19]],"date-time":"2021-10-19T06:05:11Z","timestamp":1634623511000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10822-020-00355-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,19]]},"references-count":106,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["355"],"URL":"https:\/\/doi.org\/10.1007\/s10822-020-00355-5","relation":{},"ISSN":["0920-654X","1573-4951"],"issn-type":[{"value":"0920-654X","type":"print"},{"value":"1573-4951","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,19]]},"assertion":[{"value":"14 August 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 October 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 October 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The authors declare no competing financial interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}