Research Article

Implicit solvent models for flexible protein–protein docking by molecular dynamics simulation

  1. Ting Wang1,*,
  2. Rebecca C. Wade1,2

Article first published online: 19 NOV 2002

DOI: 10.1002/prot.10248

Issue

Proteins: Structure, Function, and Bioinformatics

Proteins: Structure, Function, and Bioinformatics

Volume 50, Issue 1, pages 158–169, 1 January 2003

Additional Information

How to Cite

Wang, T. and Wade, R. C. (2003), Implicit solvent models for flexible protein–protein docking by molecular dynamics simulation. Proteins: Structure, Function, and Bioinformatics, 50: 158–169. doi: 10.1002/prot.10248

Author Information

  1. 1

    European Media Laboratory, Heidelberg, Germany

  2. 2

    European Molecular Biology Laboratory, Heidelberg, Germany

*European Media Laboratory, Schloss-Wolfsbrunnenweg 33, 69118 Heidelberg, Germany

Publication History

  1. Issue published online: 19 NOV 2002
  2. Article first published online: 19 NOV 2002
  3. Manuscript Accepted: 22 JUL 2002
  4. Manuscript Received: 16 APR 2002

Funded by

  • Human Frontiers in Science Program. Grant Number: RG0234/2000-M
  • Klaus Tschira Stiftung
  • DAAD fellowship

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Keywords:

  • molecular dynamics simulation;
  • protein stability;
  • implicit solvent model;
  • generalized Born model;
  • protein docking

Abstract

The suitability of three implicit solvent models for flexible protein–protein docking by procedures using molecular dynamics simulation is investigated. The three models are (i) the generalized Born (GB) model implemented in the program AMBER6.0; (ii) a distance-dependent dielectric (DDD) model; and (iii) a surface area-dependent model that we have parameterized and call the NPSA model. This is a distance-dependent dielectric model modified by neutralizing the ionizable side-chains and adding a surface area-dependent solvation term. These solvent models were first tested in molecular dynamics simulations at 300 K of the native structures of barnase, barstar, segment B1 of protein G, and three WW domains. These protein structures display a range of secondary structure contents and stabilities. Then, to investigate the performance of the implicit solvent models in protein docking, molecular dynamics simulations of barnase/barstar complexation, as well as PIN1 WW domain/peptide complexation, were conducted, starting from separated unbound structures. The simulations show that the NPSA model has significant advantages over the DDD and GB models in maintaining the native structures of the proteins and providing more accurate docked complexes. Proteins 2003;50:158–169. © 2002 Wiley-Liss, Inc.

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