How sensitive are nanosecond molecular dynamics simulations of proteins to changes in the force field?

Alessandra Villa, Hao Fan, Tsjerk Wassenaar, Alan E. Mark*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

16 Citations (Scopus)

Abstract

The sensitivity of molecular dynamics simulations to variations in the force field has been examined in relation to a set of 36 structures corresponding to 31 proteins simulated by using different versions of the GROMOS force field. The three parameter sets used (43a1, 53a5, and 53a6) differ significantly in regard to the nonbonded parameters for polar functional groups and their ability to reproduce the correct solvation and partitioning behavior of small molecular analogues of the amino acid side chains. Despite the differences in the force field parameters no major differences could be detected in a wide range of structural properties such as the root-mean-square deviation from the experimental structure, radii of gyration, solvent accessible surface, secondary structure, or hydrogen bond propensities on a 5 to 10 ns time scale. The small differences that were observed correlated primarily with the presence of charged residues as opposed to residues that differed most between the parameter sets. The work highlights the variation that can be observed in nanosecond simulations of protein systems and implications of this for force field validation, as well as for the analysis of protein simulations in general.

Original languageEnglish
Pages (from-to)6015-6025
Number of pages11
JournalJournal of Physical Chemistry B
Volume111
Issue number21
DOIs
Publication statusPublished - 31-May-2007

Keywords

  • DNA-BINDING DOMAIN
  • 3-DIMENSIONAL SOLUTION STRUCTURE
  • X-RAY CRYSTALLOGRAPHY
  • HELIX-COIL TRANSITION
  • SIDE-CHAIN ANALOGS
  • CRYSTAL-STRUCTURE
  • CONDENSED-PHASE
  • TERMINAL DOMAIN
  • NUCLEIC-ACIDS
  • NMR STRUCTURE

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