Oversampling Free Energy Perturbation Simulation in Determination of the Ligand-Binding Free Energy.

摘要: Determination of the ligand-binding affinity is an extremely interesting problem. Normally, free energy perturbation (FEP) method provides appropriate result. However, it great interest to improve accuracy and precision this method. In context, temperature replica exchange molecular dynamics implementation FEP computational approach, which we call (REP) was proposed. particular, during REP simulations, system can easily escape from being trapped in local minima by exchanging configurations with high temperatures, resulting significant improvement protein-ligand binding calculations. The distribution decoupling enlarged, its mean values were decreased. This results changes magnitude calculated energies as well alteration mechanism. Moreover, correlation coefficient respect experiment ( RREP = 0.85 ± 0.15) significantly boosted comparison one RFEP 0.64 ± 0.30). Furthermore, root-mean-square error (RMSE) also smaller than FEP, RMSEREP 4.28 ± 0.69 versus RMSEFEP 5.80 ± 1.11 kcal/mol, respectively. © 2019 Wiley Periodicals, Inc.