CJCU

Chem. J. Chinese Universities ›› 2017, Vol. 38 ›› Issue (11): 2070.doi: 10.7503/cjcu20170212

• Physical Chemistry • Previous Articles     Next Articles

Effect of Force Fields and Water Models on EGFRvⅢ-MR1(scFv)Complex by Molecular Dynamics Simulation, MM-PBSA Calculation, and ITC Experiment†

REN Jiayi1, YANG Zhiwei2, ZHENG Nianjue3,4, LI Junqi3, YANG Chunlong4, LIN Shujian3, YANG Bing3, HUANG Junqing1, LIAO Huaxin3,6, YUAN Xiaohui3,6,7,*(), OU Shiyi5,*()   

  1. 1. Chinese Medicine College, Jinan University, Guangzhou 510632, China
    2. School of Science, Xian Jiaotong University, Xi'an 710049, China
    3. Institute of Biomedicine, Jinan University, Guangzhou 510632, China
    4. Shunde Hospital of Guangzhou University of Chinese Medicine, Shunde 528300, China
    5. Department of Food Science and Engineering, Jinan University, Guangzhou 510632, China
    6. Guangdong Provincial Key Laboratory of Bioengineering Medicine, Guangzhou 510632, China
    7. National Engineering Research Center of Genetic Medicine, Guangzhou 510632, China
  • Received:2017-04-11 Online:2017-11-10 Published:2017-10-30
  • Contact: YUAN Xiaohui,OU Shiyi E-mail:yuanhui1024@gmail.com;tosy@jnu.edu.cn
  • Supported by:
    † Supported by the National Natural Science Foundation of China(No.31400795), the Guangdong Innovative and Entrepreneurial Research Team Program, China(No.2013Y113), the Pearl River S&T Nova Program of Guangzhou, China(No.201506010097), the Opening Project of Guangdong Province Key Laboratory of Computational Science at the Sun Yat-sen University, China(No.2016004) and the Operating Fund of Guangdong Provincial Key Laboratory of Bioengineering Medicine, China(No.2014B03, 0301050)

RichHTML

PDF (PC)

Abstract:

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.

Key words: Single-chain variable fragment(scFv), Molecular dynamics(MD) simulation, Molecular mechanics/Poisson-Boltzmann surface area(MM-PBSA), Isothermal titration calorimetry(ITC), Root mean square deviation(RMSD)

CLC Number: 

TrendMD: