{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T13:13:33Z","timestamp":1788441213273,"version":"build-2803163510"},"reference-count":74,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T00:00:00Z","timestamp":1770768000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T00:00:00Z","timestamp":1770768000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Mol Model"],"published-print":{"date-parts":[[2026,3]]},"DOI":"10.1007\/s00894-026-06642-6","type":"journal-article","created":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T05:59:17Z","timestamp":1770789557000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Exploring FDA-approved small molecules for their potential as PD-1\/PD-L1 inhibitors: integrating computational screening with experimental testing"],"prefix":"10.1007","volume":"32","author":[{"given":"Shishir","family":"Rohit","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehul","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umang","family":"Shah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alkesh","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nehangi","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajeshwari","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anish","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,11]]},"reference":[{"key":"6642_CR1","doi-asserted-by":"publisher","first-page":"638","DOI":"10.2174\/0113892037297012240408063250","volume":"25","author":"S Rohit","year":"2024","unstructured":"Rohit S, Patel M, Jagtap Y et al (2024) Structural insights of PD-1\/PD-L1 axis: an in silico approach. Curr Protein Pept Sci 25:638\u2013650. https:\/\/doi.org\/10.2174\/0113892037297012240408063250","journal-title":"Curr Protein Pept Sci"},{"key":"6642_CR2","doi-asserted-by":"publisher","first-page":"S87","DOI":"10.3747\/co.27.5223","volume":"27","author":"K Esfahani","year":"2020","unstructured":"Esfahani K, Roudaia L, Buhlaiga N et al (2020) A review of cancer immunotherapy: from the past, to the present, to the future. Curr Oncol 27:S87\u2013S97. https:\/\/doi.org\/10.3747\/co.27.5223","journal-title":"Curr Oncol"},{"key":"6642_CR3","doi-asserted-by":"publisher","DOI":"10.3390\/jcm12134301","volume":"12","author":"NA Alturki","year":"2023","unstructured":"Alturki NA (2023) Review of the immune checkpoint inhibitors in the context of cancer treatment. J Clin Med 12:4301. https:\/\/doi.org\/10.3390\/jcm12134301","journal-title":"J Clin Med"},{"key":"6642_CR4","doi-asserted-by":"publisher","first-page":"3044","DOI":"10.3390\/curroncol29050247","volume":"29","author":"Y Shiravand","year":"2022","unstructured":"Shiravand Y, Khodadadi F, Kashani SMA et al (2022) Immune checkpoint inhibitors in cancer therapy. Curr Oncol 29:3044\u20133060. https:\/\/doi.org\/10.3390\/curroncol29050247","journal-title":"Curr Oncol"},{"key":"6642_CR5","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01088","volume":"11","author":"Y Chen","year":"2020","unstructured":"Chen Y, Pei Y, Luo J et al (2020) Looking for the optimal PD-1\/PD-L1 inhibitor in cancer treatment: a comparison in basic structure, function, and clinical practice. Front Immunol 11:1088. https:\/\/doi.org\/10.3389\/fimmu.2020.01088","journal-title":"Front Immunol"},{"key":"6642_CR6","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1002\/med.21530","volume":"39","author":"J Yang","year":"2019","unstructured":"Yang J, Hu L (2019) Immunomodulators targeting the PD-1\/PD-L1 protein-protein interaction: from antibodies to small molecules. Med Res Rev 39:265\u2013301. https:\/\/doi.org\/10.1002\/med.21530","journal-title":"Med Res Rev"},{"key":"6642_CR7","unstructured":"PD-1: an inhibitory immunoreceptor involved in peripheral tolerance: Trends in Immunology. https:\/\/www.cell.com\/trends\/immunology\/abstract\/S1471-4906(01)01888-9. Accessed 17 Nov 2025"},{"key":"6642_CR8","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1016\/j.apsb.2019.09.006","volume":"10","author":"X Chen","year":"2020","unstructured":"Chen X, Pan X, Zhang W et al (2020) Epigenetic strategies synergize with PD-L1\/PD-1 targeted cancer immunotherapies to enhance antitumor responses. Acta Pharm Sin B 10:723\u2013733. https:\/\/doi.org\/10.1016\/j.apsb.2019.09.006","journal-title":"Acta Pharm Sin B"},{"key":"6642_CR9","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1038\/nrc3239","volume":"12","author":"DM Pardoll","year":"2012","unstructured":"Pardoll DM (2012) The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 12:252\u2013264. https:\/\/doi.org\/10.1038\/nrc3239","journal-title":"Nat Rev Cancer"},{"key":"6642_CR10","doi-asserted-by":"publisher","first-page":"2187","DOI":"10.1084\/jem.20100643","volume":"207","author":"K Sakuishi","year":"2010","unstructured":"Sakuishi K, Apetoh L, Sullivan JM et al (2010) Targeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunity. J Exp Med 207:2187\u20132194. https:\/\/doi.org\/10.1084\/jem.20100643","journal-title":"J Exp Med"},{"key":"6642_CR11","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1038\/nrd.2015.35","volume":"15","author":"A Hoos","year":"2016","unstructured":"Hoos A (2016) Development of immuno-oncology drugs \u2014 from CTLA4 to PD1 to the next generations. Nat Rev Drug Discov 15:235\u2013247. https:\/\/doi.org\/10.1038\/nrd.2015.35","journal-title":"Nat Rev Drug Discov"},{"key":"6642_CR12","doi-asserted-by":"publisher","first-page":"1350","DOI":"10.1126\/science.aar4060","volume":"359","author":"A Ribas","year":"2018","unstructured":"Ribas A, Wolchok JD (2018) Cancer immunotherapy using checkpoint blockade. Science 359:1350\u20131355. https:\/\/doi.org\/10.1126\/science.aar4060","journal-title":"Science"},{"key":"6642_CR13","doi-asserted-by":"publisher","first-page":"11614","DOI":"10.1021\/acs.jmedchem.1c00957","volume":"64","author":"D Muszak","year":"2021","unstructured":"Muszak D, Surmiak E, Plewka J et al (2021) Terphenyl-based small-molecule inhibitors of programmed cell death-1\/programmed death-ligand 1 protein\u2013protein interaction. J Med Chem 64:11614\u201311636. https:\/\/doi.org\/10.1021\/acs.jmedchem.1c00957","journal-title":"J Med Chem"},{"key":"6642_CR14","doi-asserted-by":"publisher","first-page":"2837","DOI":"10.3390\/cells12242837","volume":"12","author":"M Delgado","year":"2023","unstructured":"Delgado M, Garcia-Sanz JA (2023) Therapeutic monoclonal antibodies against cancer: present and future. Cells 12:2837. https:\/\/doi.org\/10.3390\/cells12242837","journal-title":"Cells"},{"key":"6642_CR15","doi-asserted-by":"publisher","DOI":"10.1186\/s12929-024-00996-w","volume":"31","author":"M Kumar","year":"2024","unstructured":"Kumar M, Jalota A, Sahu SK, Haque S (2024) Therapeutic antibodies for the prevention and treatment of cancer. J Biomed Sci 31:6. https:\/\/doi.org\/10.1186\/s12929-024-00996-w","journal-title":"J Biomed Sci"},{"key":"6642_CR16","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1038\/nrc2051","volume":"7","author":"I Melero","year":"2007","unstructured":"Melero I, Hervas-Stubbs S, Glennie M et al (2007) Immunostimulatory monoclonal antibodies for cancer therapy. Nat Rev Cancer 7:95\u2013106. https:\/\/doi.org\/10.1038\/nrc2051","journal-title":"Nat Rev Cancer"},{"key":"6642_CR17","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1080\/13543776.2018.1512706","volume":"28","author":"S Shaabani","year":"2018","unstructured":"Shaabani S, Huizinga HPS, Butera R et al (2018) A patent review on PD-1\/PD-L1 antagonists: small molecules, peptides, and macrocycles (2015-2018). Expert Opin Ther Pat 28:665\u2013678. https:\/\/doi.org\/10.1080\/13543776.2018.1512706","journal-title":"Expert Opin Ther Pat"},{"key":"6642_CR18","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1021\/acsmedchemlett.5b00148","volume":"6","author":"AF Abdel-Magid","year":"2015","unstructured":"Abdel-Magid AF (2015) Inhibitors of the PD-1\/PD-L1 pathway can mobilize the immune system: an innovative potential therapy for cancer and chronic infections. ACS Med Chem Lett 6:489\u2013490. https:\/\/doi.org\/10.1021\/acsmedchemlett.5b00148","journal-title":"ACS Med Chem Lett"},{"key":"6642_CR19","doi-asserted-by":"publisher","DOI":"10.3390\/molecules24152804","volume":"24","author":"B Musielak","year":"2019","unstructured":"Musielak B, Kocik J, Skalniak L et al (2019) CA-170 \u2013 a potent small-molecule PD-L1 inhibitor or not? Molecules 24:2804. https:\/\/doi.org\/10.3390\/molecules24152804","journal-title":"Molecules"},{"key":"6642_CR20","unstructured":"Bristol-Myers Squibb (2018) Randomized, double-blinded, placebo-controlled, single ascending dose study to evaluate the pharmacokinetics, safety, tolerability and pharmacodynamics of BMS-986189 in healthy subjects. clinicaltrials.gov. https:\/\/clinicaltrials.gov\/study\/NCT02739373?cond=NCT02739373&rank=1. Accessed 26 Jan 2026"},{"key":"6642_CR21","doi-asserted-by":"publisher","first-page":"1222","DOI":"10.1038\/s41467-021-21410-1","volume":"12","author":"J-J Park","year":"2021","unstructured":"Park J-J, Thi EP, Carpio VH et al (2021) Checkpoint inhibition through small molecule-induced internalization of programmed death-ligand 1. Nat Commun 12:1222. https:\/\/doi.org\/10.1038\/s41467-021-21410-1","journal-title":"Nat Commun"},{"key":"6642_CR22","unstructured":"Gilead Sciences (2022) A Phase 1b&#x2F;2 Dose Escalation&#x2F;Expansion study to evaluate the safety, tolerability, pharmacokinetics, and efficacy of GS-4224 in subjects with advanced solid tumors. clinicaltrials.gov. https:\/\/clinicaltrials.gov\/study\/NCT04049617cond=NCT04049617&rank=1. Accessed 26 Jan 2026"},{"key":"6642_CR23","doi-asserted-by":"publisher","first-page":"4083","DOI":"10.1021\/acs.jmedchem.3c02362","volume":"67","author":"Y Xu","year":"2024","unstructured":"Xu Y, Du H, Guo W et al (2024) Discovery of highly potent small-molecule PD-1\/PD-L1 inhibitors with a novel scaffold for cancer immunotherapy. J Med Chem 67:4083\u20134099. https:\/\/doi.org\/10.1021\/acs.jmedchem.3c02362","journal-title":"J Med Chem"},{"key":"6642_CR24","doi-asserted-by":"publisher","first-page":"1161","DOI":"10.1039\/D3MD00655G","volume":"15","author":"J Xu","year":"2024","unstructured":"Xu J, Kong Y, Zhu P et al (2024) Progress in small-molecule inhibitors targeting PD-L1. RSC Med Chem 15:1161\u20131175. https:\/\/doi.org\/10.1039\/D3MD00655G","journal-title":"RSC Med Chem"},{"key":"6642_CR25","doi-asserted-by":"publisher","unstructured":"Pinzi L, Bisi N, Rastelli G (2024) How drug repurposing can advance drug discovery: challenges and opportunities. Front Drug Discov 4:. https:\/\/doi.org\/10.3389\/fddsv.2024.1460100","DOI":"10.3389\/fddsv.2024.1460100"},{"key":"6642_CR26","doi-asserted-by":"publisher","DOI":"10.1007\/s11886-021-01484-5","volume":"23","author":"E Kort","year":"2021","unstructured":"Kort E, Jovinge S (2021) Drug repurposing: claiming the full benefit from drug development. Curr Cardiol Rep 23:62. https:\/\/doi.org\/10.1007\/s11886-021-01484-5","journal-title":"Curr Cardiol Rep"},{"key":"6642_CR27","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1134\/S1068162023020139","volume":"49","author":"VS Kulkarni","year":"2023","unstructured":"Kulkarni VS, Alagarsamy V, Solomon VR et al (2023) Drug repurposing: an effective tool in modern drug discovery. Russ J Bioorg Chem 49:157\u2013166. https:\/\/doi.org\/10.1134\/S1068162023020139","journal-title":"Russ J Bioorg Chem"},{"key":"6642_CR28","unstructured":"Selleckchem.com - Bioactive Compounds Expert (Bioactive Compounds,Compound Libraries). https:\/\/www.selleckchem.com\/. Accessed 10 Oct 2024"},{"key":"6642_CR29","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1007\/s10822-013-9644-8","volume":"27","author":"G Madhavi Sastry","year":"2013","unstructured":"Madhavi Sastry G, Adzhigirey M, Day T et al (2013) Protein and ligand preparation: parameters, protocols, and influence on virtual screening enrichments. J Comput Aided Mol Des 27:221\u2013234. https:\/\/doi.org\/10.1007\/s10822-013-9644-8","journal-title":"J Comput Aided Mol Des"},{"key":"6642_CR30","doi-asserted-by":"publisher","first-page":"5857","DOI":"10.1021\/acs.jmedchem.7b00293","volume":"60","author":"K Guzik","year":"2017","unstructured":"Guzik K, Zak KM, Grudnik P et al (2017) Small-molecule inhibitors of the programmed cell death-1\/programmed death-ligand 1 (PD-1\/PD-L1) interaction via transiently induced protein states and dimerization of PD-L1. J Med Chem 60:5857\u20135867. https:\/\/doi.org\/10.1021\/acs.jmedchem.7b00293","journal-title":"J Med Chem"},{"key":"6642_CR31","first-page":"273","volume-title":"Progress in Medicinal Chemistry","author":"F Stanzione","year":"2021","unstructured":"Stanzione F, Giangreco I, Cole JC (2021) Chapter Four - Use of molecular docking computational tools in drug discovery. In: Witty DR, Cox B (eds) Progress in Medicinal Chemistry. Elsevier, pp 273\u2013343"},{"key":"6642_CR32","doi-asserted-by":"publisher","first-page":"2693","DOI":"10.1002\/prot.23099","volume":"79","author":"OV Stroganov","year":"2011","unstructured":"Stroganov OV, Novikov FN, Zeifman AA et al (2011) TSAR, a new graph\u2013theoretical approach to computational modeling of protein side-chain flexibility: modeling of ionization properties of proteins. Proteins Struct Funct Bioinform 79:2693\u20132710. https:\/\/doi.org\/10.1002\/prot.23099","journal-title":"Proteins Struct Funct Bioinform"},{"key":"6642_CR33","doi-asserted-by":"publisher","first-page":"2371","DOI":"10.1021\/ci800166p","volume":"48","author":"OV Stroganov","year":"2008","unstructured":"Stroganov OV, Novikov FN, Stroylov VS et al (2008) Lead finder: an approach to improve accuracy of protein\u2212ligand docking, binding energy estimation, and virtual screening. J Chem Inf Model 48:2371\u20132385. https:\/\/doi.org\/10.1021\/ci800166p","journal-title":"J Chem Inf Model"},{"key":"6642_CR34","doi-asserted-by":"publisher","first-page":"2090","DOI":"10.1021\/ci200034y","volume":"51","author":"FN Novikov","year":"2011","unstructured":"Novikov FN, Zeifman AA, Stroganov OV et al (2011) CSAR scoring challenge reveals the need for new concepts in estimating protein\u2013ligand binding affinity. J Chem Inf Model 51:2090\u20132096. https:\/\/doi.org\/10.1021\/ci200034y","journal-title":"J Chem Inf Model"},{"key":"6642_CR35","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1007\/s10822-012-9549-y","volume":"26","author":"FN Novikov","year":"2012","unstructured":"Novikov FN, Stroylov VS, Zeifman AA et al (2012) Lead finder docking and virtual screening evaluation with Astex and DUD test sets. J Comput Aided Mol Des 26:725\u2013735. https:\/\/doi.org\/10.1007\/s10822-012-9549-y","journal-title":"J Comput Aided Mol Des"},{"key":"6642_CR36","doi-asserted-by":"publisher","first-page":"1223","DOI":"10.1007\/s00894-009-0633-8","volume":"16","author":"FN Novikov","year":"2010","unstructured":"Novikov FN, Stroylov VS, Stroganov OV, Chilov GG (2010) Improving performance of docking-based virtual screening by structural filtration. J Mol Model 16:1223\u20131230. https:\/\/doi.org\/10.1007\/s00894-009-0633-8","journal-title":"J Mol Model"},{"key":"6642_CR37","first-page":"396","volume":"7","author":"AN Jain","year":"2004","unstructured":"Jain AN (2004) Virtual screening in lead discovery and optimization. Curr Opin Drug Discov Devel 7:396\u2013403","journal-title":"Curr Opin Drug Discov Devel"},{"key":"6642_CR38","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1005659","volume":"13","author":"P Eastman","year":"2017","unstructured":"Eastman P, Swails J, Chodera JD et al (2017) OpenMM 7: rapid development of high performance algorithms for molecular dynamics. PLoS Comput Biol 13:e1005659. https:\/\/doi.org\/10.1371\/journal.pcbi.1005659","journal-title":"PLoS Comput Biol"},{"key":"6642_CR39","doi-asserted-by":"publisher","DOI":"10.1063\/1.4872239","volume":"140","author":"MF Harrach","year":"2014","unstructured":"Harrach MF, Drossel B (2014) Structure and dynamics of TIP3P, TIP4P, and TIP5P water near smooth and atomistic walls of different hydroaffinity. J Chem Phys 140:174501. https:\/\/doi.org\/10.1063\/1.4872239","journal-title":"J Chem Phys"},{"key":"6642_CR40","doi-asserted-by":"publisher","first-page":"4521","DOI":"10.1021\/acs.jcim.1c00794","volume":"61","author":"SP Kadaoluwa Pathirannahalage","year":"2021","unstructured":"Kadaoluwa Pathirannahalage SP, Meftahi N, Elbourne A et al (2021) Systematic comparison of the structural and dynamic properties of commonly used water models for molecular dynamics simulations. J Chem Inf Model 61:4521\u20134536. https:\/\/doi.org\/10.1021\/acs.jcim.1c00794","journal-title":"J Chem Inf Model"},{"key":"6642_CR41","doi-asserted-by":"publisher","first-page":"13496","DOI":"10.1080\/07391102.2023.2175376","volume":"41","author":"CC Mehta","year":"2023","unstructured":"Mehta CC, Rohit S, Patel S, Bhatt HG (2023) New molecular insights for 4H\u20131,2,4-triazole derivatives as inhibitors of tankyrase and Wnt-signaling antagonist: a molecular dynamics simulation study. J Biomol Struct Dyn 41:13496\u201313508. https:\/\/doi.org\/10.1080\/07391102.2023.2175376","journal-title":"J Biomol Struct Dyn"},{"key":"6642_CR42","doi-asserted-by":"publisher","DOI":"10.1063\/5.0040966","volume":"154","author":"AC Simmonett","year":"2021","unstructured":"Simmonett AC, Brooks BR (2021) A compression strategy for particle mesh Ewald theory. J Chem Phys 154:054112. https:\/\/doi.org\/10.1063\/5.0040966","journal-title":"J Chem Phys"},{"key":"6642_CR43","doi-asserted-by":"publisher","first-page":"2371","DOI":"10.1021\/ct900275y","volume":"5","author":"MJ Harvey","year":"2009","unstructured":"Harvey MJ, De Fabritiis G (2009) An implementation of the smooth particle mesh Ewald method on GPU hardware. J Chem Theory Comput 5:2371\u20132377. https:\/\/doi.org\/10.1021\/ct900275y","journal-title":"J Chem Theory Comput"},{"key":"6642_CR44","doi-asserted-by":"publisher","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. https:\/\/doi.org\/10.1517\/17460441.2015.1032936","journal-title":"Expert Opin Drug Discov"},{"key":"6642_CR45","unstructured":"Grace User\u2019s Guide (for Grace-5.1.22). https:\/\/plasma-gate.weizmann.ac.il\/Grace\/doc\/UsersGuide.html. Accessed 17 Nov 2025"},{"key":"6642_CR46","doi-asserted-by":"publisher","first-page":"2769","DOI":"10.1002\/cmdc.202100264","volume":"16","author":"E Fattakhova","year":"2021","unstructured":"Fattakhova E, Hofer J, DiFlumeri J et al (2021) Identification of the FDA-approved drug pyrvinium as a small-molecule inhibitor of the PD-1\/PD-L1 interaction. ChemMedChem 16:2769\u20132774. https:\/\/doi.org\/10.1002\/cmdc.202100264","journal-title":"ChemMedChem"},{"key":"6642_CR47","doi-asserted-by":"publisher","DOI":"10.1093\/nargab\/lqad114","volume":"6","author":"M Ko\u017ei\u0107","year":"2024","unstructured":"Ko\u017ei\u0107 M, Berto\u0161a B (2024) Trajectory maps: molecular dynamics visualization and analysis. NAR Genom Bioinform 6:lqad114. https:\/\/doi.org\/10.1093\/nargab\/lqad114","journal-title":"NAR Genom Bioinform"},{"key":"6642_CR48","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1007\/978-1-61779-588-6_10","volume":"857","author":"I Kufareva","year":"2012","unstructured":"Kufareva I, Abagyan R (2012) Methods of protein structure comparison. Methods Mol Biol 857:231\u2013257. https:\/\/doi.org\/10.1007\/978-1-61779-588-6_10","journal-title":"Methods Mol Biol"},{"key":"6642_CR49","doi-asserted-by":"publisher","first-page":"9418","DOI":"10.1021\/acs.jpcb.4c04901","volume":"128","author":"JA Lemkul","year":"2024","unstructured":"Lemkul JA (2024) Introductory tutorials for simulating protein dynamics with GROMACS. J Phys Chem B 128:9418\u20139435. https:\/\/doi.org\/10.1021\/acs.jpcb.4c04901","journal-title":"J Phys Chem B"},{"key":"6642_CR50","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0119264","volume":"10","author":"L Mart\u00ednez","year":"2015","unstructured":"Mart\u00ednez L (2015) Automatic identification of mobile and rigid substructures in molecular dynamics simulations and fractional structural fluctuation analysis. PLoS ONE 10:e0119264. https:\/\/doi.org\/10.1371\/journal.pone.0119264","journal-title":"PLoS ONE"},{"key":"6642_CR51","doi-asserted-by":"publisher","first-page":"1771","DOI":"10.3390\/ijms23031771","volume":"23","author":"S Rampogu","year":"2022","unstructured":"Rampogu S, Lee G, Park JS et al (2022) Molecular docking and molecular dynamics simulations discover curcumin analogue as a plausible dual inhibitor for SARS-CoV-2. Int J Mol Sci 23:1771. https:\/\/doi.org\/10.3390\/ijms23031771","journal-title":"Int J Mol Sci"},{"key":"6642_CR52","doi-asserted-by":"publisher","first-page":"570","DOI":"10.1002\/bmb.21512","volume":"49","author":"GC Justino","year":"2021","unstructured":"Justino GC, Nascimento CP, Justino MC (2021) Molecular dynamics simulations and analysis for bioinformatics undergraduate students. Biochem Mol Biol Educ 49:570\u2013582. https:\/\/doi.org\/10.1002\/bmb.21512","journal-title":"Biochem Mol Biol Educ"},{"key":"6642_CR53","doi-asserted-by":"publisher","first-page":"5061","DOI":"10.1021\/jm100112j","volume":"53","author":"C Bissantz","year":"2010","unstructured":"Bissantz C, Kuhn B, Stahl M (2010) A medicinal chemist\u2019s guide to molecular interactions. J Med Chem 53:5061\u20135084. https:\/\/doi.org\/10.1021\/jm100112j","journal-title":"J Med Chem"},{"key":"6642_CR54","doi-asserted-by":"publisher","first-page":"24","DOI":"10.12691\/ajmo-5-1-3","volume":"5","author":"MJR Yunta","year":"2017","unstructured":"Yunta MJR (2017) It is important to compute intramolecular hydrogen bonding in drug design? Am J Model Optim 5:24\u201357. https:\/\/doi.org\/10.12691\/ajmo-5-1-3","journal-title":"Am J Model Optim"},{"key":"6642_CR55","doi-asserted-by":"crossref","unstructured":"Hubbard RE, Kamran Haider M (2010) Hydrogen bonds in proteins: role and strength. In: Encyclopedia of life sciences. John Wiley & Sons, Ltd","DOI":"10.1002\/9780470015902.a0003011.pub2"},{"key":"6642_CR56","doi-asserted-by":"publisher","first-page":"14261","DOI":"10.1021\/acs.jmedchem.2c01147","volume":"65","author":"PW Kenny","year":"2022","unstructured":"Kenny PW (2022) Hydrogen-bond donors in drug design. J Med Chem 65:14261\u201314275. https:\/\/doi.org\/10.1021\/acs.jmedchem.2c01147","journal-title":"J Med Chem"},{"key":"6642_CR57","doi-asserted-by":"publisher","first-page":"13815","DOI":"10.1021\/jacs.2c04986","volume":"144","author":"J Shao","year":"2022","unstructured":"Shao J, Kuiper BP, Thunnissen A-MWH et al (2022) The role of tryptophan in \u03c0 interactions in proteins: an experimental approach. J Am Chem Soc 144:13815\u201313822. https:\/\/doi.org\/10.1021\/jacs.2c04986","journal-title":"J Am Chem Soc"},{"key":"6642_CR58","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.bioorg.2013.06.005","volume":"49","author":"S Vaideeswaran","year":"2013","unstructured":"Vaideeswaran S, Ramaiah S (2013) Investigations on the role of \u03c0\u2013\u03c0 interactions and \u03c0\u2013\u03c0 networks in eNOS and nNOS proteins. Bioorg Chem 49:16\u201323. https:\/\/doi.org\/10.1016\/j.bioorg.2013.06.005","journal-title":"Bioorg Chem"},{"key":"6642_CR59","doi-asserted-by":"publisher","first-page":"1504S","DOI":"10.1093\/jn\/137.6.1504S","volume":"137","author":"DA Dougherty","year":"2007","unstructured":"Dougherty DA (2007) Cation-pi interactions involving aromatic amino acids. J Nutr 137:1504S-1508S. https:\/\/doi.org\/10.1093\/jn\/137.6.1504S","journal-title":"J Nutr"},{"key":"6642_CR60","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1007\/s12013-013-9573-0","volume":"67","author":"V Sivasakthi","year":"2013","unstructured":"Sivasakthi V, Anbarasu A, Ramaiah S (2013) \u03c0-\u03c0 interactions in structural stability: role in RNA binding proteins. Cell Biochem Biophys 67:853\u2013863. https:\/\/doi.org\/10.1007\/s12013-013-9573-0","journal-title":"Cell Biochem Biophys"},{"key":"6642_CR61","doi-asserted-by":"publisher","first-page":"8687","DOI":"10.1021\/acs.jpcb.4c04774","volume":"128","author":"R Calinsky","year":"2024","unstructured":"Calinsky R, Levy Y (2024) Aromatic residues in proteins: re-evaluating the geometry and energetics of \u03c0\u2013\u03c0, cation\u2212\u03c0, and CH\u2212\u03c0 interactions. J Phys Chem B 128:8687\u20138700. https:\/\/doi.org\/10.1021\/acs.jpcb.4c04774","journal-title":"J Phys Chem B"},{"key":"6642_CR62","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1016\/j.csbj.2019.06.022","volume":"17","author":"X Ban","year":"2019","unstructured":"Ban X, Lahiri P, Dhoble AS et al (2019) Evolutionary stability of salt bridges hints its contribution to stability of proteins. Comput Struct Biotechnol J 17:895\u2013903. https:\/\/doi.org\/10.1016\/j.csbj.2019.06.022","journal-title":"Comput Struct Biotechnol J"},{"key":"6642_CR63","doi-asserted-by":"publisher","first-page":"898","DOI":"10.1002\/prot.22927","volume":"79","author":"JE Donald","year":"2011","unstructured":"Donald JE, Kulp DW, DeGrado WF (2011) Salt bridges: geometrically specific, designable interactions. Proteins Struct Funct Bioinform 79:898\u2013915. https:\/\/doi.org\/10.1002\/prot.22927","journal-title":"Proteins Struct Funct Bioinform"},{"key":"6642_CR64","doi-asserted-by":"publisher","first-page":"842","DOI":"10.1016\/j.jmb.2006.11.061","volume":"366","author":"AV Gribenko","year":"2007","unstructured":"Gribenko AV, Makhatadze GI (2007) Role of the charge-charge interactions in defining stability and halophilicity of the CspB proteins. J Mol Biol 366:842\u2013856. https:\/\/doi.org\/10.1016\/j.jmb.2006.11.061","journal-title":"J Mol Biol"},{"key":"6642_CR65","doi-asserted-by":"publisher","first-page":"3514","DOI":"10.1021\/ct200465z","volume":"7","author":"DJ Huggins","year":"2011","unstructured":"Huggins DJ, Marsh M, Payne MC (2011) Thermodynamic properties of water molecules at a protein-protein interaction surface. J Chem Theory Comput 7:3514\u20133522. https:\/\/doi.org\/10.1021\/ct200465z","journal-title":"J Chem Theory Comput"},{"key":"6642_CR66","doi-asserted-by":"publisher","first-page":"9170","DOI":"10.1021\/ja034729u","volume":"125","author":"GA Papoian","year":"2003","unstructured":"Papoian GA, Ulander J, Wolynes PG (2003) Role of water mediated interactions in protein-protein recognition landscapes. J Am Chem Soc 125:9170\u20139178. https:\/\/doi.org\/10.1021\/ja034729u","journal-title":"J Am Chem Soc"},{"key":"6642_CR67","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1007\/978-1-62703-658-0_11","volume":"1084","author":"CC David","year":"2014","unstructured":"David CC, Jacobs DJ (2014) Principal component analysis: a method for determining the essential dynamics of proteins. Methods Mol Biol 1084:193\u2013226. https:\/\/doi.org\/10.1007\/978-1-62703-658-0_11","journal-title":"Methods Mol Biol"},{"key":"6642_CR68","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1016\/j.drudis.2017.01.005","volume":"22","author":"A Giuliani","year":"2017","unstructured":"Giuliani A (2017) The application of principal component analysis to drug discovery and biomedical data. Drug Discov Today 22:1069\u20131076. https:\/\/doi.org\/10.1016\/j.drudis.2017.01.005","journal-title":"Drug Discov Today"},{"key":"6642_CR69","doi-asserted-by":"publisher","DOI":"10.1016\/j.compbiomed.2024.109245","volume":"183","author":"S Moradi","year":"2024","unstructured":"Moradi S, Nowroozi A, Aryaei Nezhad M et al (2024) A review on description dynamics and conformational changes of proteins using combination of principal component analysis and molecular dynamics simulation. Comput Biol Med 183:109245. https:\/\/doi.org\/10.1016\/j.compbiomed.2024.109245","journal-title":"Comput Biol Med"},{"key":"6642_CR70","doi-asserted-by":"publisher","first-page":"22129","DOI":"10.1039\/C6CP03670H","volume":"18","author":"F Chen","year":"2016","unstructured":"Chen F, Liu H, Sun H et al (2016) Assessing the performance of the MM\/PBSA and MM\/GBSA methods. 6. Capability to predict protein\u2013protein binding free energies and re-rank binding poses generated by protein\u2013protein docking. Phys Chem Chem Phys 18:22129\u201322139. https:\/\/doi.org\/10.1039\/C6CP03670H","journal-title":"Phys Chem Chem Phys"},{"key":"6642_CR71","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1021\/ci100275a","volume":"51","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. 1. The accuracy of binding free energy calculations based on molecular dynamics simulations. J Chem Inf Model 51:69\u201382. https:\/\/doi.org\/10.1021\/ci100275a","journal-title":"J Chem Inf Model"},{"key":"6642_CR72","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1016\/S1089-3261(03)00031-X","volume":"7","author":"TJ Davern","year":"2003","unstructured":"Davern TJ, Bass NM (2003) Leukotriene antagonists. Clin Liver Dis 7:501\u2013512. https:\/\/doi.org\/10.1016\/S1089-3261(03)00031-X","journal-title":"Clin Liver Dis"},{"key":"6642_CR73","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1161\/HYPERTENSIONAHA.115.05138","volume":"65","author":"NM Kaplan","year":"2015","unstructured":"Kaplan NM (2015) Indapamide: is it the better diuretic for hypertension? Hypertension 65:983\u2013984. https:\/\/doi.org\/10.1161\/HYPERTENSIONAHA.115.05138","journal-title":"Hypertension"},{"key":"6642_CR74","doi-asserted-by":"publisher","first-page":"567","DOI":"10.2165\/00003495-200969050-00005","volume":"69","author":"KP Garnock-Jones","year":"2009","unstructured":"Garnock-Jones KP, Keam SJ (2009) Eltrombopag. Drugs 69:567\u2013576. https:\/\/doi.org\/10.2165\/00003495-200969050-00005","journal-title":"Drugs"}],"container-title":["Journal of Molecular Modeling"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00894-026-06642-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00894-026-06642-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00894-026-06642-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T00:09:35Z","timestamp":1772842175000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00894-026-06642-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,11]]},"references-count":74,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["6642"],"URL":"https:\/\/doi.org\/10.1007\/s00894-026-06642-6","relation":{},"ISSN":["1610-2940","0948-5023"],"issn-type":[{"value":"1610-2940","type":"print"},{"value":"0948-5023","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,11]]},"assertion":[{"value":"12 August 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 January 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 February 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The author declares that Artificial Intelligence was not used for data analysis and visualization in this study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Statement of usage of artificial intelligence"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"65"}}