{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T02:51:56Z","timestamp":1771210316627,"version":"3.50.1"},"reference-count":76,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,7,12]],"date-time":"2020-07-12T00:00:00Z","timestamp":1594512000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2020,7,12]],"date-time":"2020-07-12T00:00:00Z","timestamp":1594512000000},"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":["Netw Model Anal Health Inform Bioinforma"],"published-print":{"date-parts":[[2020,12]]},"DOI":"10.1007\/s13721-020-00244-9","type":"journal-article","created":{"date-parts":[[2020,7,12]],"date-time":"2020-07-12T06:02:57Z","timestamp":1594533777000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Structure-based virtual screening, molecular docking and dynamics studies of natural product and classical inhibitors against human dihydrofolate reductase"],"prefix":"10.1007","volume":"9","author":[{"given":"Elnaz Hosseininezhadian","family":"Koushki","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Solmaz","family":"Abolghasemi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adriano","family":"Mollica","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mojtaba","family":"Aghaeepoor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seyedeh Sara","family":"Moosavi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiako","family":"Farshadfar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bayazid","family":"Hasanpour","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Babisandz","family":"Feyzi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fatemeh","family":"Abdi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sako","family":"Mirzaie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,7,12]]},"reference":[{"key":"244_CR1","doi-asserted-by":"crossref","first-page":"4942","DOI":"10.1021\/jm990017w","volume":"42","author":"Bemis GW Ajay","year":"1999","unstructured":"Ajay Bemis GW, Murcko MA (1999) Designing libraries with CNS activity. J Med Chem 42:4942\u20134951","journal-title":"J Med Chem"},{"key":"244_CR2","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.jmb.2007.01.085","volume":"368","author":"M Arai","year":"2007","unstructured":"Arai M, Kondrashkina E, Kayatekin C, Matthews CR, Iwakura M, Bilsel O (2007) Microsecond hydrophobic collapse in the folding of Escherichia coli dihydrofolate reductase, an \u03b1\/\u03b2-type protein. J Mol Biol 368:219\u2013229","journal-title":"J Mol Biol"},{"key":"244_CR3","doi-asserted-by":"crossref","first-page":"9236","DOI":"10.3390\/ijms12129236","volume":"12","author":"M Arooj","year":"2011","unstructured":"Arooj M, Thangapandian S, John S, Hwang S, Park JK, Lee KW (2011) 3D QSAR pharmacophore modeling, in silico screening, and density functional theory (DFT) approaches for identification of human chymase inhibitors. Int J Mol Sci 12:9236\u20139264","journal-title":"Int J Mol Sci"},{"key":"244_CR4","doi-asserted-by":"crossref","first-page":"5642","DOI":"10.1021\/ja9000135","volume":"131","author":"K Arora","year":"2009","unstructured":"Arora K, Brooks Iii CL (2009) Functionally important conformations of the Met20 loop in dihydrofolate reductase are populated by rapid thermal fluctuations. J Am Chem Soc 131:5642\u20135647","journal-title":"J Am Chem Soc"},{"key":"244_CR5","doi-asserted-by":"crossref","first-page":"W257","DOI":"10.1093\/nar\/gky318","volume":"46","author":"P Banerjee","year":"2018","unstructured":"Banerjee P, Eckert AO, Schrey AK, Preissner R (2018) ProTox-II: a webserver for the prediction of toxicity of chemicals. Nucleic Acids Res 46:W257\u2013W263","journal-title":"Nucleic Acids Res"},{"key":"244_CR6","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 Bioinform 73:765\u2013783","journal-title":"Proteins Struct Funct Bioinform"},{"key":"244_CR7","doi-asserted-by":"crossref","first-page":"651","DOI":"10.2165\/11318430-000000000-00000","volume":"70","author":"C Bebrone","year":"2010","unstructured":"Bebrone C, Lassaux P, Vercheval L, Sohier J-S, Jehaes A, Sauvage E et al (2010) Current challenges in antimicrobial chemotherapy. Drugs 70:651\u2013679","journal-title":"Drugs"},{"key":"244_CR8","doi-asserted-by":"crossref","first-page":"5648","DOI":"10.1063\/1.464913","volume":"98","author":"AD Becke","year":"1993","unstructured":"Becke AD (1993) Density-functional thermochemistry. III. The role of exact exchange. J Chem Phys 98:5648\u20135652","journal-title":"J Chem Phys"},{"key":"244_CR9","doi-asserted-by":"crossref","first-page":"13650","DOI":"10.1016\/S0021-9258(18)33497-5","volume":"257","author":"JT Bolin","year":"1982","unstructured":"Bolin JT, Filman DJ, Matthews DA, Hamlin RC, Kraut J (1982) Crystal structures of Escherichia coli and Lactobacillus casei dihydrofolate reductase refined at 1.7\u00a0A resolution. I. General features and binding of methotrexate. J Biol Chem 257:13650\u201313662","journal-title":"J Biol Chem"},{"key":"244_CR10","doi-asserted-by":"crossref","first-page":"014101","DOI":"10.1063\/1.2408420","volume":"126","author":"G Bussi","year":"2007","unstructured":"Bussi G, Donadio D, Parrinello M (2007) Canonical sampling through velocity rescaling. J Chem Phys 126:014101","journal-title":"J Chem Phys"},{"key":"244_CR11","doi-asserted-by":"publisher","unstructured":"Calvert H (2003) Pemetrexed (Alimta): a promising new agent for the treatment of breast cancer. Semin Oncol 30(2 Suppl 3):2\u20135. https:\/\/doi.org\/10.1053\/sonc.2003.37267","DOI":"10.1053\/sonc.2003.37267"},{"key":"244_CR12","doi-asserted-by":"crossref","first-page":"10667","DOI":"10.1021\/j100026a034","volume":"99","author":"HA Carlson","year":"1995","unstructured":"Carlson HA, Jorgensen WL (1995) An extended linear response method for determining free energies of hydration. J Phys Chem 99:10667\u201310673","journal-title":"J Phys Chem"},{"key":"244_CR13","doi-asserted-by":"crossref","first-page":"3844","DOI":"10.1021\/jm0208875","volume":"45","author":"A Cavalli","year":"2002","unstructured":"Cavalli A, Poluzzi E, De Ponti F, Recanatini M (2002) Toward a pharmacophore for drugs inducing the long QT syndrome: insights from a CoMFA study of HERG K+ channel blockers. J Med Chem 45:3844\u20133853","journal-title":"J Med Chem"},{"key":"244_CR14","doi-asserted-by":"crossref","first-page":"3933","DOI":"10.1016\/S0021-9258(17)43186-3","volume":"259","author":"M-J Chen","year":"1984","unstructured":"Chen M-J, Shimada T, Moulton AD, Cline A, Humphries RK, Maizel J et al (1984) The functional human dihydrofolate reductase gene. J Biol Chem 259:3933\u20133943","journal-title":"J Biol Chem"},{"key":"244_CR15","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1208\/s12248-012-9322-0","volume":"14","author":"T Cheng","year":"2012","unstructured":"Cheng T, Li Q, Zhou Z, Wang Y, Bryant SH (2012) Structure-based virtual screening for drug discovery: a problem-centric review. AAPS J 14:133\u2013141","journal-title":"AAPS J"},{"key":"244_CR16","doi-asserted-by":"crossref","first-page":"4756","DOI":"10.1021\/bi00069a009","volume":"32","author":"E Chu","year":"1993","unstructured":"Chu E, Takimoto CH, Voeller D, Grem JL, Allegra CJ (1993) Specific binding of human dihydrofolate reductase protein to dihydrofolate reductase messenger RNA in vitro. Biochemistry 32:4756\u20134760","journal-title":"Biochemistry"},{"key":"244_CR17","first-page":"483","volume":"7","author":"V Cody","year":"1992","unstructured":"Cody V, Luft J, Ciszak E, Kalman T, Freisheim J (1992) Crystal structure determination at 2.3\u00a0A of recombinant human dihydrofolate reductase ternary complex with NADPH and methotrexate-gamma-tetrazole. Anti Cancer Drug Des 7:483\u2013491","journal-title":"Anti Cancer Drug Des"},{"key":"244_CR18","doi-asserted-by":"crossref","first-page":"13897","DOI":"10.1021\/bi971711l","volume":"36","author":"V Cody","year":"1997","unstructured":"Cody V, Galitsky N, Luft JR, Pangborn W, Rosowsky A, Blakley RL (1997) Comparison of two independent crystal structures of human dihydrofolate reductase ternary complexes reduced with nicotinamide adenine dinucleotide phosphate and the very tight-binding inhibitor PT523. Biochemistry 36:13897\u201313903","journal-title":"Biochemistry"},{"key":"244_CR19","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1107\/S0907444904030422","volume":"61","author":"V Cody","year":"2005","unstructured":"Cody V, Luft JR, Pangborn W (2005) Understanding the role of Leu22 variants in methotrexate resistance: comparison of wild-type and Leu22Arg variant mouse and human dihydrofolate reductase ternary crystal complexes with methotrexate and NADPH. Acta Crystallogr D Biol Crystallogr 61:147\u2013155","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"key":"244_CR20","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\u00b7 log (N) method for Ewald sums in large systems. J Chem Phys 98:10089\u201310092","journal-title":"J Chem Phys"},{"key":"244_CR21","doi-asserted-by":"crossref","first-page":"1753","DOI":"10.1021\/jm00366a018","volume":"26","author":"EF Elslager","year":"1983","unstructured":"Elslager EF, Johnson JL, Werbel LM (1983) Folate antagonists. 20. Synthesis and antitumor and antimalarial properties of trimetrexate and related 6-[(phenylamino) methyl]-2,4-quinazolinediamines. J Med Chem 26:1753\u20131760","journal-title":"J Med Chem"},{"key":"244_CR22","doi-asserted-by":"crossref","first-page":"12317","DOI":"10.1021\/bi971026e","volume":"36","author":"EA Ercikan-Abali","year":"1997","unstructured":"Ercikan-Abali EA, Banerjee D, Waltham MC, Skacel N, Scotto KW, Bertino JR (1997) Dihydrofolate reductase protein inhibits its own translation by binding to dihydrofolate reductase mRNA sequences within the coding region. Biochemistry 36:12317\u201312322","journal-title":"Biochemistry"},{"key":"244_CR23","doi-asserted-by":"crossref","first-page":"4519","DOI":"10.1021\/la00011a056","volume":"11","author":"U Essmann","year":"1995","unstructured":"Essmann U, Perera L, Berkowitz ML (1995) The origin of the hydration interaction of lipid bilayers from MD simulation of dipalmitoylphosphatidylcholine membranes in gel and liquid crystalline phases. Langmuir 11:4519\u20134531","journal-title":"Langmuir"},{"key":"244_CR24","first-page":"218","volume":"22","author":"DT Felson","year":"1995","unstructured":"Felson DT, Chernoff M, Anderson J, Weinblatt M, Furst D, Schmid F et al (1995) The effect of age and renal function on the efficacy and toxicity of methotrexate in rheumatoid arthritis. J Rheumatol 22:218\u2013223","journal-title":"J Rheumatol"},{"key":"244_CR25","doi-asserted-by":"crossref","first-page":"3219","DOI":"10.1016\/0040-4020(80)80168-2","volume":"36","author":"J Gasteiger","year":"1980","unstructured":"Gasteiger J, Marsili M (1980) Iterative partial equalization of orbital electronegativity\u2014a rapid access to atomic charges. Tetrahedron 36:3219\u20133228","journal-title":"Tetrahedron"},{"key":"244_CR26","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1517\/17460441.2015.1032936","volume":"10","author":"S Genheden","year":"2015","unstructured":"Genheden S, Ryde U (2015) The MM\/PBSA and MM\/GBSA methods to estimate ligand-binding affinities. Expert Opin Drug Discov 10:449\u2013461","journal-title":"Expert Opin Drug Discov"},{"key":"244_CR27","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1021\/jm00177a025","volume":"23","author":"EM Grivsky","year":"1980","unstructured":"Grivsky EM, Lee S, Sigel CW, Duch DS, Nichol CA (1980) Synthesis and antitumor activity of 2,4-diamino-6-(2,5-dimethoxybenzyl)-5-methylpyrido[2,3-d]pyrimidine. J Med Chem 23:327\u2013329","journal-title":"J Med Chem"},{"key":"244_CR28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1471-2105-7-293","volume":"7","author":"S G\u00fcnther","year":"2006","unstructured":"G\u00fcnther S, Senger C, Michalsky E, Goede A, Preissner R (2006) Representation of target-bound drugs by computed conformers: implications for conformational libraries. BMC Bioinform 7:1","journal-title":"BMC Bioinform"},{"key":"244_CR29","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1159\/000342735","volume":"30","author":"HH Herfarth","year":"2013","unstructured":"Herfarth HH, Long MD, Isaacs KL (2013) Methotrexate: underused and ignored? Dig Dis 30:112\u2013118","journal-title":"Dig Dis"},{"key":"244_CR30","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1002\/(SICI)1096-987X(199709)18:12<1463::AID-JCC4>3.0.CO;2-H","volume":"18","author":"B Hess","year":"1997","unstructured":"Hess B, Bekker H, Berendsen HJ, Fraaije JG (1997) LINCS: a linear constraint solver for molecular simulations. J Comput Chem 18:1463\u20131472","journal-title":"J Comput Chem"},{"key":"244_CR31","first-page":"50","volume":"84","author":"B Hileman","year":"2006","unstructured":"Hileman B (2006) Accounting for R&D-Many doubt the $800 million pharmaceutical price tag. Chem Eng News 84:50","journal-title":"Chem Eng News"},{"key":"244_CR32","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1002\/jcc.21666","volume":"32","author":"T Hou","year":"2011","unstructured":"Hou T, Wang J, Li Y, Wang W (2011) Assessing the performance of the MM\/PBSA and MM\/GBSA methods: II. The accuracy of ranking poses generated from docking. J Comput Chem 32:866\u2013877","journal-title":"J Comput Chem"},{"key":"244_CR33","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.jdcr.2015.06.003","volume":"1","author":"M-C Hsu","year":"2015","unstructured":"Hsu M-C, Chen C-C (2015) Low-dose methotrexate-induced ulcerated psoriatic plaques: a rare case. JAAD Case Rep 1:264\u2013266","journal-title":"JAAD Case Rep"},{"key":"244_CR34","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\u00a014:33\u201338","journal-title":"J Mol Graph"},{"key":"244_CR35","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1021\/ci049714+","volume":"45","author":"JJ Irwin","year":"2005","unstructured":"Irwin JJ, Shoichet BK (2005) ZINC-a free database of commercially available compounds for virtual screening. J Chem Inf Model 45:177\u2013182","journal-title":"J Chem Inf Model"},{"key":"244_CR36","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1056\/NEJM198311033091805","volume":"309","author":"J Jolivet","year":"1983","unstructured":"Jolivet J, Cowan KH, Curt GA, Clendeninn NJ, Chabner BA (1983) The pharmacology and clinical use of methotrexate. N Engl J Med 309:1094\u20131104","journal-title":"N Engl J Med"},{"key":"244_CR37","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 79:926\u2013935","journal-title":"J Chem Phys"},{"key":"244_CR38","doi-asserted-by":"crossref","first-page":"11225","DOI":"10.1021\/ja9621760","volume":"118","author":"WL Jorgensen","year":"1996","unstructured":"Jorgensen WL, Maxwell DS, Tirado-Rives J (1996) Development and testing of the OPLS all-atom force field on conformational energetics and properties of organic liquids. J Am Chem Soc 118:11225\u201311236","journal-title":"J Am Chem Soc"},{"key":"244_CR39","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.jtbi.2017.03.010","volume":"420","author":"M Karami","year":"2017","unstructured":"Karami M, Jalali C, Mirzaie S (2017) Combined virtual screening, MMPBSA, molecular docking and dynamics studies against deadly anthrax: an in silico effort to inhibit Bacillus anthracis nucleoside hydrolase. J Theor Biol 420:180\u2013189","journal-title":"J Theor Biol"},{"key":"244_CR40","doi-asserted-by":"crossref","first-page":"1514","DOI":"10.1023\/A:1015040217741","volume":"16","author":"J Kelder","year":"1999","unstructured":"Kelder J, Grootenhuis PD, Bayada DM, Delbressine LP, Ploemen J-P (1999) Polar molecular surface as a dominating determinant for oral absorption and brain penetration of drugs. Pharm Res 16:1514\u20131519","journal-title":"Pharm Res"},{"key":"244_CR41","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/S0022-2836(02)00469-2","volume":"320","author":"AE Klon","year":"2002","unstructured":"Klon AE, H\u00e9roux A, Ross LJ, Pathak V, Johnson CA, Piper JR et al (2002) Atomic structures of human dihydrofolate reductase complexed with NADPH and two lipophilic antifolates at 1.09\u00a0\u00c5 and 1.05\u00a0\u00c5 resolution. J Mol Biol 320:677\u2013693","journal-title":"J Mol Biol"},{"key":"244_CR42","doi-asserted-by":"crossref","first-page":"2395","DOI":"10.1021\/cr00023a004","volume":"93","author":"P Kollman","year":"1993","unstructured":"Kollman P (1993) Free energy calculations: applications to chemical and biochemical phenomena. Chem Rev 93:2395\u20132417","journal-title":"Chem Rev"},{"key":"244_CR43","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1021\/ar000033j","volume":"33","author":"PA Kollman","year":"2000","unstructured":"Kollman PA, Massova I, Reyes C, Kuhn B, Huo S, Chong L et al (2000) Calculating structures and free energies of complex molecules: combining molecular mechanics and continuum models. Acc Chem Res 33:889\u2013897","journal-title":"Acc Chem Res"},{"key":"244_CR44","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1007\/s10858-005-1475-z","volume":"33","author":"NV Kovalevskaya","year":"2005","unstructured":"Kovalevskaya NV, Smurnyy YD, Polshakov VI, Birdsall B, Bradbury AF, Frenkiel T et al (2005) Solution structure of human dihydrofolate reductase in its complex with trimethoprim and NADPH. J Biomol NMR 33:69\u201372","journal-title":"J Biomol NMR"},{"key":"244_CR45","doi-asserted-by":"crossref","first-page":"353","DOI":"10.7326\/0003-4819-110-5-353","volume":"110","author":"RA Kozarek","year":"1989","unstructured":"Kozarek RA, Patterson DJ, Gelfand MD, Botoman VA, Ball TJ, Wilske KR (1989) Methotrexate induces clinical and histologic remission in patients with refractory inflammatory bowel disease. Ann Intern Med 110:353\u2013356","journal-title":"Ann Intern Med"},{"key":"244_CR46","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1039\/C3MB70537D","volume":"10","author":"K Kumar","year":"2014","unstructured":"Kumar K, Anbarasu A, Ramaiah S (2014) Molecular docking and molecular dynamics studies on \u03b2-lactamases and penicillin binding proteins. Mol BioSyst 10:891\u2013900","journal-title":"Mol BioSyst"},{"key":"244_CR47","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.1021\/ci500020m","volume":"54","author":"R Kumari","year":"2014","unstructured":"Kumari R, Kumar R, Lynn A (2014) g_mmpbsa: a GROMACS tool for high-throughput MM-PBSA calculations. J Chem Inf Model 54:1951\u20131962","journal-title":"J Chem Inf Model"},{"key":"244_CR48","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1103\/PhysRevB.37.785","volume":"37","author":"C Lee","year":"1988","unstructured":"Lee C, Yang W, Parr RG (1988) Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. Phys Rev B 37:785","journal-title":"Phys Rev B"},{"key":"244_CR49","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1021\/ci980411n","volume":"39","author":"JM Luco","year":"1999","unstructured":"Luco JM (1999) Prediction of the brain\u2013blood distribution of a large set of drugs from structurally derived descriptors using partial least-squares (PLS) modeling. J Chem Inf Comput Sci 39:396\u2013404","journal-title":"J Chem Inf Comput Sci"},{"key":"244_CR50","doi-asserted-by":"crossref","first-page":"5032","DOI":"10.1073\/pnas.0500699102","volume":"102","author":"D McElheny","year":"2005","unstructured":"McElheny D, Schnell JR, Lansing JC, Dyson HJ, Wright PE (2005) Defining the role of active-site loop fluctuations in dihydrofolate reductase catalysis. Proc Natl Acad Sci USA 102:5032\u20135037","journal-title":"Proc Natl Acad Sci USA"},{"key":"244_CR51","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1016\/j.compbiomed.2011.12.009","volume":"42","author":"S Mirzaie","year":"2012","unstructured":"Mirzaie S, Rafii F, Yasunaga K, Yoshunaga K, Sepehrizadeh Z, Kanno S et al (2012) Prediction of the mode of interaction between monoterpenes and the nitroreductase from Enterobacter cloacae by docking simulation. Comput Biol Med 42:414\u2013421","journal-title":"Comput Biol Med"},{"key":"244_CR52","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1080\/07391102.2014.924877","volume":"33","author":"S Mirzaie","year":"2015","unstructured":"Mirzaie S, Najafi K, Hakhamaneshi MS, Shahverdi AR, Fathi F (2015) Investigation for antimicrobial resistance-modulating activity of diethyl malate and 1-methyl malate against beta-lactamase class A from Bacillus licheniformis by molecular dynamics, in vitro and in vivo studies. J Biomol Struct Dyn 33:1016\u20131026","journal-title":"J Biomol Struct Dyn"},{"key":"244_CR53","doi-asserted-by":"publisher","unstructured":"Mollica A, Mirzaie S, Costante R, Carradori S, Macedonio G, Stefanucci A et al (2015) Exploring the biological consequences of conformational changes in aspartame models containing constrained analogues of phenylalanine. J Enzym Inhib Med Chem 31(6):953\u2013963. https:\/\/doi.org\/10.3109\/14756366.2015.1076811","DOI":"10.3109\/14756366.2015.1076811"},{"key":"244_CR54","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/0091-6749(88)90291-6","volume":"81","author":"M Mullarkey","year":"1988","unstructured":"Mullarkey M, Andrade W, Blumenstein B, Bailey G (1988) Methotrexate in the treatment of corticosteroid-dependent asthma: a double-blind crossover study with follow-up. J Allergy Clin Immunol 81:182","journal-title":"J Allergy Clin Immunol"},{"key":"244_CR55","doi-asserted-by":"crossref","first-page":"7182","DOI":"10.1063\/1.328693","volume":"52","author":"M Parrinello","year":"1981","unstructured":"Parrinello M, Rahman A (1981) Polymorphic transitions in single crystals: a new molecular dynamics method. J Appl Phys 52:7182\u20137190","journal-title":"J Appl Phys"},{"key":"244_CR56","doi-asserted-by":"crossref","first-page":"75","DOI":"10.2174\/1570163054064675","volume":"2","author":"SJ Potts","year":"2005","unstructured":"Potts SJ, Edwards DJ, Hoffman R (2005) Challenges of target\/compound data integration from disease to chemistry: a case study of dihydrofolate reductase inhibitors. Curr Drug Discov Technol 2:75\u201387","journal-title":"Curr Drug Discov Technol"},{"key":"244_CR57","doi-asserted-by":"crossref","first-page":"1726","DOI":"10.1021\/ct9006986","volume":"6","author":"P S\u00f6derhjelm","year":"2010","unstructured":"S\u00f6derhjelm P, Kongsted J, Ryde U (2010) Ligand affinities estimated by quantum chemical calculations. J Chem Theory Comput 6:1726\u20131737","journal-title":"J Chem Theory Comput"},{"key":"244_CR58","doi-asserted-by":"crossref","first-page":"13481","DOI":"10.1073\/pnas.172501499","volume":"99","author":"PT Rajagopalan","year":"2002","unstructured":"Rajagopalan PT, Zhang Z, McCourt L, Dwyer M, Benkovic SJ, Hammes GG (2002) Interaction of dihydrofolate reductase with methotrexate: ensemble and single-molecule kinetics. Proc Natl Acad Sci USA 99:13481\u201313486","journal-title":"Proc Natl Acad Sci USA"},{"key":"244_CR59","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.micpath.2016.12.003","volume":"103","author":"S Rajamanikandan","year":"2017","unstructured":"Rajamanikandan S, Jeyakanthan J, Srinivasan P (2017) Discovery of potent inhibitors targeting Vibrio harveyi LuxR through shape and e-pharmacophore based virtual screening and its biological evaluation. Microb Pathog 103:40\u201356","journal-title":"Microb Pathog"},{"key":"244_CR60","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1038\/nchem.2479","volume":"8","author":"T Rodrigues","year":"2016","unstructured":"Rodrigues T, Reker D, Schneider P, Schneider G (2016) Counting on natural products for drug design. Nat Chem 8:531\u2013541","journal-title":"Nat Chem"},{"key":"244_CR61","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1021\/bi962337c","volume":"36","author":"MR Sawaya","year":"1997","unstructured":"Sawaya MR, Kraut J (1997) Loop and subdomain movements in the mechanism of Escherichia coli dihydrofolate reductase: crystallographic evidence. Biochemistry 36:586\u2013603","journal-title":"Biochemistry"},{"key":"244_CR63","first-page":"1164","volume":"14","author":"G Searles","year":"1987","unstructured":"Searles G, McKendry R (1987) Methotrexate pneumonitis in rheumatoid arthritis: potential risk factors. Four case reports and a review of the literature. J Rheumatol 14:1164\u20131171","journal-title":"J Rheumatol"},{"key":"244_CR64","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1080\/0892702031000065782","volume":"29","author":"P Sompornpisut","year":"2003","unstructured":"Sompornpisut P, Wijitkosoom A, Parasuk V, Sirawaraporn W (2003) Molecular dynamics simulation of the human apo-dihydrofolate reductase: an investigation of an unstable enzyme. Mol Simul 29:111\u2013121","journal-title":"Mol Simul"},{"key":"244_CR65","doi-asserted-by":"crossref","first-page":"429","DOI":"10.2165\/00002018-200023050-00006","volume":"23","author":"RB Stein","year":"2000","unstructured":"Stein RB, Hanauer SB (2000) Comparative tolerability of treatments for inflammatory bowel disease. Drug Saf 23:429\u2013448","journal-title":"Drug Saf"},{"key":"244_CR66","doi-asserted-by":"crossref","first-page":"22035","DOI":"10.1039\/C4CP03179B","volume":"16","author":"H Sun","year":"2014","unstructured":"Sun H, Li Y, Shen M, Tian S, Xu L, Pan P et al (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 16:22035\u201322045","journal-title":"Phys Chem Chem Phys"},{"key":"244_CR67","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1021\/ci6004993","volume":"47","author":"R Teramoto","year":"2007","unstructured":"Teramoto R, Fukunishi H (2007) Supervised consensus scoring for docking and virtual screening. J Chem Inf Model 47:526\u2013534","journal-title":"J Chem Inf Model"},{"key":"244_CR68","doi-asserted-by":"crossref","first-page":"2018","DOI":"10.1021\/ci400178h","volume":"53","author":"RD Tosso","year":"2013","unstructured":"Tosso RD, Andujar SA, Gutierrez L, Angelina E, Rodr\u00edguez R, Nogueras M et al (2013) Molecular modeling study of dihydrofolate reductase inhibitors. Molecular dynamics simulations, quantum mechanical calculations, and experimental corroboration. J Chem Inf Model 53:2018\u20132032","journal-title":"J Chem Inf Model"},{"key":"244_CR69","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","volume":"31","author":"O Trott","year":"2010","unstructured":"Trott O, Olson AJ (2010) AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem 31:455\u2013461","journal-title":"J Comput Chem"},{"key":"244_CR70","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1002\/jcc.20291","volume":"26","author":"D Van Der Spoel","year":"2005","unstructured":"Van Der Spoel D, Lindahl E, Hess B, Groenhof G, Mark AE, Berendsen HJ (2005) GROMACS: fast, flexible, and free. J Comput Chem 26:1701\u20131718","journal-title":"J Comput Chem"},{"key":"244_CR71","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.jmgm.2005.12.005","volume":"25","author":"J Wang","year":"2006","unstructured":"Wang J, Wang W, Kollman PA, Case DA (2006a) Automatic atom type and bond type perception in molecular mechanical calculations. J Mol Graph Model 25:247\u2013260","journal-title":"J Mol Graph Model"},{"key":"244_CR72","doi-asserted-by":"crossref","first-page":"287","DOI":"10.2174\/157340906778226454","volume":"2","author":"J Wang","year":"2006","unstructured":"Wang J, Hou T, Xu X (2006b) Recent advances in free energy calculations with a combination of molecular mechanics and continuum models. Curr Comput Aided Drug Des 2:287\u2013306","journal-title":"Curr Comput Aided Drug Des"},{"key":"244_CR73","doi-asserted-by":"crossref","first-page":"ii94","DOI":"10.1136\/ard.62.suppl_2.ii94","volume":"62","author":"M Weinblatt","year":"2003","unstructured":"Weinblatt M (2003) Rheumatoid arthritis in 2003: where are we now with treatment? Ann Rheum Dis 62:ii94\u2013ii96","journal-title":"Ann Rheum Dis"},{"key":"244_CR74","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1001\/archderm.1971.04000210010003","volume":"104","author":"GD Weinstein","year":"1971","unstructured":"Weinstein GD, Goldfaden G, Frost P (1971) Methotrexate: mechanism of action on DNA synthesis in psoriasis. Arch Dermatol 104:236\u2013243","journal-title":"Arch Dermatol"},{"key":"244_CR75","doi-asserted-by":"crossref","first-page":"1490","DOI":"10.1023\/A:1011930411574","volume":"15","author":"M Yazdanian","year":"1998","unstructured":"Yazdanian M, Glynn SL, Wright JL, Hawi A (1998) Correlating partitioning and Caco-2 cell permeability of structurally diverse small molecular weight compounds. Pharm Res 15:1490\u20131494","journal-title":"Pharm Res"},{"key":"244_CR76","doi-asserted-by":"crossref","first-page":"17284","DOI":"10.3390\/ijms151017284","volume":"15","author":"D Zhan","year":"2014","unstructured":"Zhan D, Yu L, Jin H, Guan S, Han W (2014) Molecular modeling and MM-PBSA free energy analysis of endo-1,4-\u03b2-xylanase from Ruminococcus albus 8. Int J Mol Sci 15:17284\u201317303","journal-title":"Int J Mol Sci"},{"key":"244_CR77","doi-asserted-by":"crossref","first-page":"44651","DOI":"10.1038\/srep44651","volume":"7","author":"D Zhang","year":"2017","unstructured":"Zhang D, Lazim R (2017) Application of conventional molecular dynamics simulation in evaluating the stability of apomyoglobin in urea solution. Sci Rep 7:44651","journal-title":"Sci Rep"}],"container-title":["Network Modeling Analysis in Health Informatics and Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13721-020-00244-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s13721-020-00244-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13721-020-00244-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,9]],"date-time":"2024-08-09T22:59:27Z","timestamp":1723244367000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s13721-020-00244-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,12]]},"references-count":76,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["244"],"URL":"https:\/\/doi.org\/10.1007\/s13721-020-00244-9","relation":{},"ISSN":["2192-6662","2192-6670"],"issn-type":[{"value":"2192-6662","type":"print"},{"value":"2192-6670","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,12]]},"assertion":[{"value":"17 August 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 May 2020","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 May 2020","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 July 2020","order":4,"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 that they have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"This article does not contain any studies with human participants or animals performed by any of the authors.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}],"article-number":"49"}}