Binding selectivity-dependent molecular mechanism of inhibitors towards CDK2 and CDK6 investigated by multiple short molecular dynamics and free energy landscapes

References

• Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100(1):57–70.
   PubMed Web of Science ®Google Scholar
• Manning G, Whyte DB, Martinez R, Hunter T, Sudarsanam S. The protein kinase complement of the human genome. Science. 2002;298(5600):1912–1934.
   PubMed Web of Science ®Google Scholar
• Wang X, Deng K, Wang C, Li Y, Wang T, Huang Z, Ma Y, Sun P, Shi Y, Yang S, et al. Novel CDKs inhibitors for the treatment of solid tumour by simultaneously regulating the cell cycle and transcription control. J Enzyme Inhib Med Chem. 2020;35(1):414–423.
   PubMed Web of Science ®Google Scholar
• Lim S, Kaldis P. Cdks, cyclins and CKIs: roles beyond cell cycle regulation. Development. 2013;140(15):3079–3093.
   PubMed Web of Science ®Google Scholar
• Eldehna WM, Maklad RM, Almahli H, Al-Warhi T, Elkaeed EB, Abourehab MAS, Abdel-Aziz HA, El Kerdawy AM. Identification of 3-(piperazinylmethyl)benzofuran derivatives as novel type II CDK2 inhibitors: design, synthesis, biological evaluation, and in silico insights. J Enzyme Inhib Med Chem. 2022;37(1):1227–1240.
   PubMed Web of Science ®Google Scholar
• Bačević K, Lossaint G, Achour TN, Georget V, Fisher D, Dulić V. Cdk2 strengthens the intra-S checkpoint and counteracts cell cycle exit induced by DNA damage. Sci Rep. 2017;7(1):13429.
   PubMedGoogle Scholar
• Nebenfuehr S, Kollmann K, Sexl V. The role of CDK6 in cancer. Int J Cancer. 2020;147(11):2988–2995.
   PubMed Web of Science ®Google Scholar
• Bo L, Wei B, Wang Z, Kong D, Gao Z, Miao Z. Bioinformatics analysis of the CDK2 functions in neuroblastoma. Mol Med Rep. 2018;17(3):3951–3959.
   PubMed Web of Science ®Google Scholar
• Christodoulou MS, Caporuscio F, Restelli V, Carlino L, Cannazza G, Costanzi E, Citti C, Lo Presti L, Pisani P, Battistutta R, et al. Probing an allosteric pocket of CDK2 with small molecules. ChemMedChem. 2017;12(1):33–41.
   PubMed Web of Science ®Google Scholar
• Teng M, Jiang J, He Z, Kwiatkowski NP, Donovan KA, Mills CE, Victor C, Hatcher JM, Fischer ES, Sorger PK, et al. Development of CDK2 and CDK5 dual degrader TMX-2172. Angew Chem Int Ed Engl. 2020;59(33):13865–13870.
   PubMed Web of Science ®Google Scholar
• Liu X, Liu S, Piao C, Zhang Z, Zhang X, Jiang Y, Kong C. Non-metabolic function of MTHFD2 activates CDK2 in bladder cancer. Cancer Sci. 2021;112(12):4909–4919.
   PubMed Web of Science ®Google Scholar
• Cicenas J, Valius M. The CDK inhibitors in cancer research and therapy. J Cancer Res Clin Oncol. 2011;137(10):1409–1418.
   PubMed Web of Science ®Google Scholar
• Whittaker SR, Barlow C, Martin MP, Mancusi C, Wagner S, Self A, Barrie E, Te Poele R, Sharp S, Brown N, et al. Molecular profiling and combinatorial activity of CCT068127: a potent CDK2 and CDK9 inhibitor. Mol Oncol. 2018;12(3):287–304.
   PubMed Web of Science ®Google Scholar
• Wood DJ, Lopez-Fernandez JD, Knight LE, Al-Khawaldeh I, Gai C, Lin S, Martin MP, Miller DC, Cano C, Endicott JA, et al. FragLites—minimal, halogenated fragments displaying pharmacophore doublets. An efficient approach to druggability assessment and hit generation. J Med Chem. 2019;62(7):3741–3752.
   PubMed Web of Science ®Google Scholar
• Chen J, Wang X, Zhang JZH, Zhu T. Effect of substituents in different positions of aminothiazole hinge-binding scaffolds on inhibitor–CDK2 association probed by interaction entropy method. ACS Omega. 2018;3(12):18052–18064.
   Web of Science ®Google Scholar
• Zhao J, Yin B, Sun H, Pang L, Chen J. Identifying hot spots of inhibitor-CDK2 bindings by computational alanine scanning. Chem Phys Lett. 2020;747:137329.
   Web of Science ®Google Scholar
• Liang SS, Liu XG, Cui YX, Zhang SL, Zhang QG, Chen JZ. Molecular mechanism concerning conformational changes of CDK2 mediated by binding of inhibitors using molecular dynamics simulations and principal component analysis. SAR QSAR Environ Res. 2021;32(7):573–594.
   Web of Science ®Google Scholar
• Chen J, Pang L, Wang W, Wang L, Zhang JZH, Zhu T. Decoding molecular mechanism of inhibitor bindings to CDK2 using molecular dynamics simulations and binding free energy calculations. J Biomol Struct Dyn. 2020;38(4):985–996.
   PubMed Web of Science ®Google Scholar
• Mandour AA, Nassar IF, Abdel Aal MT, Shahin MAE, El-Sayed WA, Hegazy M, Yehia AM, Ismail A, Hagras M, Elkaeed EB, et al. Synthesis, biological evaluation, and in silico studies of new CDK2 inhibitors based on pyrazolo[3,4-d]pyrimidine and pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine scaffold with apoptotic activity. J Enzyme Inhib Med Chem. 2022;37(1):1957–1973.
   PubMedGoogle Scholar
• Duan L, Feng G, Wang X, Wang L, Zhang Q. Effect of electrostatic polarization and bridging water on CDK2–ligand binding affinities calculated using a highly efficient interaction entropy method. Phys Chem Chem Phys. 2017;19(15):10140–10152.
   PubMed Web of Science ®Google Scholar
• Wang L, Deng Y, Knight JL, Wu Y, Kim B, Sherman W, Shelley JC, Lin T, Abel R. Modeling local structural rearrangements using FEP/REST: application to relative binding affinity predictions of CDK2 inhibitors. J Chem Theory Comput. 2013;9(2):1282–1293.
   PubMed Web of Science ®Google Scholar
• Heller G, Nebenfuehr S, Bellutti F, Ünal H, Zojer M, Scheiblecker L, Sexl V, Kollmann K. The effect of CDK6 expression on DNA methylation and DNMT3B regulation. iScience. 2020;23(10):101602.
   PubMed Web of Science ®Google Scholar
• Dutta A, Nath D, Yang Y, Le BT, Mohi G. CDK6 is a therapeutic target in myelofibrosis. Cancer Res. 2021;81(16):4332–4345.
   PubMed Web of Science ®Google Scholar
• Iris ZU, Ruth MS, Karoline K, et al. Cdk6 contributes to cytoskeletal stability in erythroid cells. Haematologica. 2017;102:995–1005.
   PubMed Web of Science ®Google Scholar
• Schmalzbauer BS, Thondanpallil T, Heller G, Schirripa A, Sperl CM, Mayer IM, Knab VM, Nebenfuehr S, Zojer M, Mueller AC, et al. CDK6 degradation is counteracted by p16INK4A and p18INK4C in AML. Cancers. 2022;14(6):1554.
   PubMed Web of Science ®Google Scholar
• Yousuf M, Khan P, Shamsi A, Shahbaaz M, Hasan GM, Haque QMR, Christoffels A, Islam A, Hassan MI. Inhibiting CDK6 activity by quercetin is an attractive strategy for cancer therapy. ACS Omega. 2020;5(42):27480–27491.
   PubMed Web of Science ®Google Scholar
• Ayaz P, Andres D, Kwiatkowski DA, Kolbe C-C, Lienau P, Siemeister G, Lücking U, Stegmann CM. Conformational adaption may explain the slow dissociation kinetics of roniciclib (BAY 1000394), a type I CDK inhibitor with kinetic selectivity for CDK2 and CDK9. ACS Chem Biol. 2016;11(6):1710–1719.
   PubMed Web of Science ®Google Scholar
• Bronner SM, Merrick KA, Murray J, Salphati L, Moffat JG, Pang J, Sneeringer CJ, Dompe N, Cyr P, Purkey H, et al. Design of a brain-penetrant CDK4/6 inhibitor for glioblastoma. Bioorg Med Chem Lett. 2019;29(16):2294–2301.
   PubMed Web of Science ®Google Scholar
• Somarelli JA, Roghani RS, Moghaddam AS, Thomas BC, Rupprecht G, Ware KE, Altunel E, Mantyh JB, Kim SY, McCall SJ, et al. A precision medicine drug discovery pipeline identifies combined CDK2 and 9 inhibition as a novel therapeutic strategy in colorectal cancer. Mol Cancer Ther. 2020;19(12):2516–2527.
   PubMed Web of Science ®Google Scholar
• Schonbrunn E, Betzi S, Alam R, Martin MP, Becker A, Han H, Francis R, Chakrasali R, Jakkaraj S, Kazi A, et al. Development of highly potent and selective diaminothiazole inhibitors of cyclin-dependent kinases. J Med Chem. 2013;56(10):3768–3782.
   PubMed Web of Science ®Google Scholar
• Goel S, Bergholz JS, Zhao JJ. Targeting CDK4 and CDK6 in cancer. Nat Rev Cancer. 2022;22(6):356–372.
   PubMed Web of Science ®Google Scholar
• Wang L, Wang Y, Sun H, Zhao J, Wang Q. Theoretical insight into molecular mechanisms of inhibitor bindings to bromodomain-containing protein 4 using molecular dynamics simulations and calculations of binding free energies. Chem Phys Lett. 2019;736:136785.
   Web of Science ®Google Scholar
• Wang Y, Wang LF, Zhang LL, Sun HB, Zhao J. Molecular mechanism of inhibitor bindings to bromodomain-containing protein 9 explored based on molecular dynamics simulations and calculations of binding free energies. SAR QSAR Environ Res. 2020;31(2):149–170.
   PubMed Web of Science ®Google Scholar
• Li G, Shen H, Zhang D, Li Y, Wang H. Coarse-grained modeling of nucleic acids using anisotropic gay–berne and electric multipole potentials. J Chem Theory Comput. 2016;12(2):676–693.
   PubMed Web of Science ®Google Scholar
• Hou T, McLaughlin WA, Wang W. Evaluating the potency of HIV-1 protease drugs to combat resistance. Proteins. 2008;71(3):1163–1174.
   PubMed Web of Science ®Google Scholar
• Yang M-J, Pang X-Q, Zhang X, Han K-L. Molecular dynamics simulation reveals preorganization of the chloroplast FtsY towards complex formation induced by GTP binding. J Struct Biol. 2011;173(1):57–66.
   PubMed Web of Science ®Google Scholar
• Hu G, Yu X, Bian Y, Cao Z, Xu S, Zhao L, Ji B, Wang W, Wang J. Atomistic analysis of ToxN and ToxI complex unbinding mechanism. Int J Mol Sci. 2018;19(11):3524.
   PubMed Web of Science ®Google Scholar
• Cong Y, Huang K, Li Y, Zhong S, Zhang JZH, Duan L. Entropic effect and residue specific entropic contribution to the cooperativity in streptavidin–biotin binding. Nanoscale. 2020;12(13):7134–7145.
   PubMed Web of Science ®Google Scholar
• Zheng G, Yang F, Fu T, Tu G, Chen Y, Yao X, Xue W, Zhu F. Computational characterization of the selective inhibition of human norepinephrine and serotonin transporters by an escitalopram scaffold. Phys Chem Chem Phys. 2018;20(46):29513–29527.
   PubMed Web of Science ®Google Scholar
• Chen J, Wang X, Pang L, Zhang JZH, Zhu T. Effect of mutations on binding of ligands to guanine riboswitch probed by free energy perturbation and molecular dynamics simulations. Nucleic Acids Res. 2019;47(13):6618–6631.
   PubMed Web of Science ®Google Scholar
• Hu G, Ma A, Wang J. Ligand selectivity mechanism and conformational changes in guanine riboswitch by molecular dynamics simulations and free energy calculations. J Chem Inf Model. 2017;57(4):918–928.
   PubMed Web of Science ®Google Scholar
• Wu EL, Han K, Zhang JZH. Selectivity of neutral/weakly basic P1 group inhibitors of thrombin and trypsin by a molecular dynamics study. Chemistry. 2008;14(28):8704–8714.
   PubMed Web of Science ®Google Scholar
• Jia X, Wang M, Shao Y, König G, Brooks BR, Zhang JZH, Mei Y. Calculations of solvation free energy through energy reweighting from molecular mechanics to quantum mechanics. J Chem Theory Comput. 2016;12(2):499–511.
   PubMed Web of Science ®Google Scholar
• Tzoupis H, Leonis G, Mavromoustakos T, Papadopoulos MG. A comparative molecular dynamics, MM–PBSA and thermodynamic integration study of saquinavir complexes with wild-type HIV-1 PR and L10I, G48V, L63P, A71V, G73S, V82A and I84V single mutants. J Chem Theory Comput. 2013;9(3):1754–1764.
   PubMed Web of Science ®Google Scholar
• Chen J, Wang X, Zhu T, Zhang Q, Zhang JZH. 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. 2015;55(9):1903–1913.
   PubMed Web of Science ®Google Scholar
• Shirts MR, Pitera JW, Swope WC, Pande VS. Extremely precise free energy calculations of amino acid side chain analogs: comparison of common molecular mechanics force fields for proteins. J Chem Phys. 2003;119(11):5740–5761.
   Web of Science ®Google Scholar
• Naïm M, Bhat S, Rankin KN, Dennis S, Chowdhury SF, Siddiqi I, Drabik P, Sulea T, Bayly CI, Jakalian A, et al. Solvated interaction energy (SIE) for scoring protein − ligand binding affinities. 1. Exploring the parameter space. J Chem Inf Model. 2007;47(1):122–133.
   PubMed Web of Science ®Google Scholar
• Gao Y, Zhu T, Chen J. Exploring drug-resistant mechanisms of I84V mutation in HIV-1 protease toward different inhibitors by thermodynamics integration and solvated interaction energy method. Chem Phys Lett. 2018;706:400–408.
   Web of Science ®Google Scholar
• Shi D, Bai Q, Zhou S, Liu X, Liu H, Yao X. Molecular dynamics simulation, binding free energy calculation and unbinding pathway analysis on selectivity difference between FKBP51 and FKBP52: insight into the molecular mechanism of isoform selectivity. Proteins. 2018;86(1):43–56.
   PubMed Web of Science ®Google Scholar
• Wang LF, Wang Y, Yang ZY, Zhao J, Sun HB, Wu SL. Revealing binding selectivity of inhibitors toward bromodomain-containing proteins 2 and 4 using multiple short molecular dynamics simulations and free energy analyses. SAR QSAR Environ Res. 2020;31(5):373–398.
   PubMed Web of Science ®Google Scholar
• Wang Y, Wu S, Wang L, Yang Z, Zhao J, Zhang L. Binding selectivity of inhibitors toward the first over the second bromodomain of BRD4: theoretical insights from free energy calculations and multiple short molecular dynamics simulations. RSC Adv. 2020;11(2):745–759.
   PubMed Web of Science ®Google Scholar
• Aldeghi M, Heifetz A, Bodkin MJ, Knapp S, Biggin PC. Predictions of ligand selectivity from absolute binding free energy calculations. J Am Chem Soc. 2017;139(2):946–957.
   PubMed Web of Science ®Google Scholar
• Tian S, Zeng J, Liu X, Chen J, Zhang JZH, Zhu T. Understanding the selectivity of inhibitors toward PI4KIIIα and PI4KIIIβ based molecular modeling. Phys Chem Chem Phys. 2019;21(39):22103–22112.
   PubMed Web of Science ®Google Scholar
• Chen J, Wang J, Yin B, Pang L, Wang W, Zhu W. 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. 2019;10(10):4303–4318.
   PubMed Web of Science ®Google Scholar
• Chen J, Liu X, Zhang S, Chen J, Sun H, Zhang L, Zhang Q. 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. 2020;22(4):2262–2275.
   PubMed Web of Science ®Google Scholar
• Caves LSD, Evanseck JD, Karplus M. Locally accessible conformations of proteins: multiple molecular dynamics simulations of crambin. Protein Sci. 1998;7(3):649–666.
   PubMed Web of Science ®Google Scholar
• Auffinger P, Westhof E. RNA hydration: three nanoseconds of multiple molecular dynamics simulations of the solvated tRNAAsp anticodon hairpin11Edited by J. Karn. J Mol Biol. 1997;269(3):326–341.
   PubMed Web of Science ®Google Scholar
• Wang L, Wang Y, Zhao J, Yu Y, Kang N, Yang Z. Theoretical exploration of the binding selectivity of inhibitors to BRD7 and BRD9 with multiple short molecular dynamics simulations. RSC Adv. 2022;12(26):16663–16676.
   PubMed Web of Science ®Google Scholar
• Chen J, Zhang S, Zeng Q, Wang W, Zhang Q, Liu X. Free energy profiles relating with conformational transition of the switch domains induced by G12 mutations in GTP-bound KRAS. Front Mol Biosci. 2022;9:912518.
   PubMed Web of Science ®Google Scholar
• Cho YS, Angove H, Brain C, Chen CHT, Cheng H, Cheng R, Chopra R, Chung K, Congreve M, Dagostin C, et al. Fragment-based discovery of 7-azabenzimidazoles as potent, highly selective, and orally active CDK4/6 inhibitors. ACS Med Chem Lett. 2012;3(6):445–449.
   PubMed Web of Science ®Google Scholar
• Amadei A, Linssen ABM, Berendsen HJC. Essential dynamics of proteins. Proteins. 1993;17(4):412–425.
   PubMed Web of Science ®Google Scholar
• Levy RM, Srinivasan AR, Olson WK, McCammon JA. Quasi-harmonic method for studying very low frequency modes in proteins. Biopolymers. 1984;23(6):1099–1112.
   PubMed Web of Science ®Google Scholar
• Chen J, Wang L, Wang W, Sun H, Pang L, Bao H. Conformational transformation of switch domains in GDP/K-Ras induced by G13 mutants: an investigation through Gaussian accelerated molecular dynamics simulations and principal component analysis. Comput Biol Med. 2021;135:104639.
   PubMed Web of Science ®Google Scholar
• Chen J, Zhang S, Wang W, Sun H, Zhang Q, Liu X. Binding of inhibitors to BACE1 affected by pH-dependent protonation: an exploration from multiple replica gaussian accelerated molecular dynamics and MM-GBSA calculations. ACS Chem Neurosci. 2021;12(14):2591–2607.
   PubMed Web of Science ®Google Scholar
• Webb B, Sali A. Comparative protein structure modeling using MODELLER in current protocols in bioinformatics. Curr Protoc Bioinformatics. 2016;54:5.6.1–5.6.37.
   PubMedGoogle Scholar
• Chen J, Wang W, Sun H, Pang L, Yin B. Mutation-mediated influences on binding of anaplastic lymphoma kinase to crizotinib decoded by multiple replica Gaussian accelerated molecular dynamics. J Comput Aided Mol Des. 2020;34(12):1289–1305.
   PubMed Web of Science ®Google Scholar
• Li H, Robertson AD, Jensen JH. Very fast empirical prediction and rationalization of protein pKa values. Proteins. 2005;61(4):704–721.
   PubMed Web of Science ®Google Scholar
• Bas DC, Rogers DM, Jensen JH. Very fast prediction and rationalization of pKa values for protein–ligand complexes. Proteins. 2008;73(3):765–783.
   PubMed Web of Science ®Google Scholar
• Salomon-Ferrer R, Case DA, Walker RC. An overview of the Amber biomolecular simulation package. WIREs Comput Mol Sci. 2013;3(2):198–210.
   Web of Science ®Google Scholar
• Case DA, Cheatham TE, Darden T, Gohlke H, Luo R, Merz KM, Onufriev A, Simmerling C, Wang B, Woods RJ, et al. The Amber biomolecular simulation programs. J Comput Chem. 2005;26(16):1668–1688.
   PubMed Web of Science ®Google Scholar
• Tian C, Kasavajhala K, Belfon KAA, Raguette L, Huang H, Migues AN, Bickel J, Wang Y, Pincay J, Wu Q, et al. ff19SB: amino-acid-specific protein backbone parameters trained against quantum mechanics energy surfaces in solution. J Chem Theory Comput. 2020;16(1):528–552.
   PubMed Web of Science ®Google Scholar
• Jorgensen WL, Chandrasekhar J, Madura JD, Impey RW, Klein ML. Comparison of simple potential functions for simulating liquid water. J Chem Phys. 1983;79(2):926–935.
   Web of Science ®Google Scholar
• Wang J, Wolf RM, Caldwell JW, Kollman PA, Case DA. Development and testing of a general amber force field. J Comput Chem. 2004;25(9):1157–1174.
   PubMed Web of Science ®Google Scholar
• Chen J, Wang J, Zeng Q, Wang W, Sun H, Wei B. Exploring the deactivation mechanism of human β2 adrenergic receptor by accelerated molecular dynamic simulations. Front Mol Biosci. 2022;9:972463.
   PubMed Web of Science ®Google Scholar
• Darden T, York D, Pedersen L. Particle mesh Ewald: an N⋅log(N) method for Ewald sums in large systems. J Chem Phys. 1993;98(12):10089–10092.
   Web of Science ®Google Scholar
• Essmann U, Perera L, Berkowitz ML, Darden T, Lee H, Pedersen LG. A smooth particle mesh Ewald method. J Chem Phys. 1995;103(19):8577–8593.
   Web of Science ®Google Scholar
• Ryckaert JP, Ciccotti G, Berendsen HJC. Numerical integration of the cartesian equations of motion of a system with constraints: molecular dynamics of n-alkanes. J Comput Phys. 1977;23(3):327–341.
   Web of Science ®Google Scholar
• Izaguirre JA, Catarello DP, Wozniak JM, Skeel RD. Langevin stabilization of molecular dynamics. J Chem Phys. 2001;114(5):2090–2098.
   Web of Science ®Google Scholar
• Götz AW, Williamson MJ, Xu D, Poole D, Le Grand S, Walker RC. Routine microsecond molecular dynamics simulations with AMBER on GPUs. 1. Generalized born. J Chem Theory Comput. 2012;8(5):1542–1555.
   PubMed Web of Science ®Google Scholar
• Salomon-Ferrer R, Götz AW, Poole D, Le Grand S, Walker RC. Routine microsecond molecular dynamics simulations with AMBER on GPUs. 2. Explicit solvent particle mesh ewald. J Chem Theory Comput. 2013;9(9):3878–3888.
   PubMed Web of Science ®Google Scholar
• Ichiye T, Karplus M. Collective motions in proteins: a covariance analysis of atomic fluctuations in molecular dynamics and normal mode simulations. Proteins. 1991;11(3):205–217.
   PubMed Web of Science ®Google Scholar
• Liang S, Liu X, Zhang S, Li M, Zhang Q, Chen J. Binding mechanism of inhibitors to SARS-CoV-2 main protease deciphered by multiple replica molecular dynamics simulations. Phys Chem Chem Phys. 2022;24(3):1743–1759.
   PubMed Web of Science ®Google Scholar
• Su J, Liu X, Zhang S, Yan F, Zhang Q, Chen J. Insight into selective mechanism of class of I-BRD9 inhibitors toward BRD9 based on molecular dynamics simulations. Chem Biol Drug Des. 2019;93(2):163–176.
   PubMed Web of Science ®Google Scholar
• Yu Z, Su H, Chen J, Hu G. Deciphering conformational changes of the GDP-bound NRAS induced by mutations G13D, Q61R, and C118S through gaussian accelerated molecular dynamic simulations. Molecules. 2022;27(17):5596.
   PubMed Web of Science ®Google Scholar
• Roe DR, Cheatham TE. PTRAJ and CPPTRAJ: software for processing and analysis of molecular dynamics trajectory data. J Chem Theory Comput. 2013;9(7):3084–3095.
   PubMed Web of Science ®Google Scholar
• Wang J, Morin P, Wang W, Kollman PA. Use of MM-PBSA in reproducing the binding free energies to HIV-1 RT of TIBO derivatives and predicting the binding mode to HIV-1 RT of efavirenz by docking and MM-PBSA. J Am Chem Soc. 2001;123(22):5221–5230.
   PubMed Web of Science ®Google Scholar
• Wang W, Kollman PA. Computational study of protein specificity: the molecular basis of HIV-1 protease drug resistance. Proc Natl Acad Sci USA. 2001;98(26):14937–14942.
   PubMed Web of Science ®Google Scholar
• Chen J, Wang W, Sun H, Pang L, Bao H. Binding mechanism of inhibitors to p38α MAP kinase deciphered by using multiple replica Gaussian accelerated molecular dynamics and calculations of binding free energies. Comput Biol Med. 2021;134:104485.
   PubMed Web of Science ®Google Scholar
• Yan F, Liu X, Zhang S, Su J, Zhang Q, Chen J. Molecular dynamics exploration of selectivity of dual inhibitors 5M7, 65X, and 65Z toward fatty acid binding proteins 4 and 5. Int J Mol Sci. 2018;19(9):2496.
   PubMed Web of Science ®Google Scholar
• Sun H, Li Y, Shen M, Tian S, Xu L, Pan P, Guan Y, Hou T. 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. 2014;16(40):22035–22045.
   PubMed Web of Science ®Google Scholar
• Sun H, Li Y, Tian S, Xu L, Hou T. 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. 2014;16(31):16719–16729.
   PubMed Web of Science ®Google Scholar
• Onufriev A, Bashford D, Case DA. Exploring protein native states and large-scale conformational changes with a modified generalized born model. Proteins. 2004;55(2):383–394.
   PubMed Web of Science ®Google Scholar
• Gohlke H, Kiel C, Case DA. Insights into protein–protein binding by binding free energy calculation and free energy decomposition for the Ras–Raf and Ras–RalGDS complexes. J Mol Biol. 2003;330(4):891–913.
   PubMed Web of Science ®Google Scholar
• Miller BR, McGee TD, Swails JM, Homeyer N, Gohlke H, Roitberg AE. MMPBSA.py: an efficient program for end-state free energy calculations. J Chem Theory Comput. 2012;8(9):3314–3321.
   PubMed Web of Science ®Google Scholar
• Frauenfelder H, Sligar SG, Wolynes PG. The energy landscapes and motions of proteins. Science. 1991;254(5038):1598–1603.
   PubMed Web of Science ®Google Scholar
• Brooks CL, Onuchic JN, Wales DJ. Taking a walk on a landscape. Science. 2001;293(5530):612–613.
   PubMed Web of Science ®Google Scholar
• Tsai CJ, Ma B, Nussinov R. Folding and binding cascades: shifts in energy landscapes. Proc Natl Acad Sci USA. 1999;96(18):9970–9972.
   PubMed Web of Science ®Google Scholar
• Chen J, Zhang S, Wang W, Pang L, Zhang Q, Liu X. Mutation-induced impacts on the switch transformations of the GDP- and GTP-bound K-Ras: insights from multiple replica gaussian accelerated molecular dynamics and free energy analysis. J Chem Inf Model. 2021;61(4):1954–1969.
   PubMed Web of Science ®Google Scholar
• Li M, Liu X, Zhang S, Liang S, Zhang Q, Chen J. Deciphering the binding mechanism of inhibitors of the SARS-CoV-2 main protease through multiple replica accelerated molecular dynamics simulations and free energy landscapes. Phys Chem Chem Phys. 2022;24(36):22129–22143.
   PubMed Web of Science ®Google Scholar
• Zhang Y, Cao Z, Zhang JZ, Xia F. Double-well ultra-coarse-grained model to describe protein conformational transitions. J Chem Theory Comput. 2020;16(10):6678–6689.
   PubMed Web of Science ®Google Scholar