Effect of Force Fields and Water Models on EGFRvⅢ-MR1(scFv) Complex by Molecular Dynamics Simulation, MM-PBSA Calculation, and ITC Experiment
© 2017, Higher Education Press. All right reserved. Six commonly used force fields and three commonly used solvent water models were employed, respectively, for EGFRvIII and its corresponding scFv antibody(MR1) complex, and total 16 antigen-antibody complex moleaular(MD) simulations were carried out. The molecular mechanics/Poisson-Boltzmann surface area(MM-PBSA) calculations were performed and the thermodynamic parameters of antigen-antibody interaction were measured by isothermal titration calorimetry(ITC) experiment. The RMSD analysis show that all the MD simulations were stable, but the binding free energy values from MM-PBSA are different under 6 force fields and 3 water models. The recommended calculation models are given by comprehensive analysis of structural changes, energy changes, consistency of experiment and combining calculation and experimental verification with two antibody humanization mutants(huMR1-2 and huMR1-G). At the same time, the calculation accuracy of different force fields and solvent water models were discussed. The conclusions of this study can be used in the subsequent antibody humanization, antibody affinity maturation, and other related computer-aided antibody drug design.
Ren, J; Yang, Z; Zheng, N; Li, J; Yang, C; Lin, S; Yang, B; Huang, J; Liao, H; Yuan, X; Ou, S
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