Sensitivity of molecular dynamics simulations to the choice of the X-ray structure used to model an enzymatic reaction

Mireia Garcia-Viloca, Tina D. Poulsen, Donald G. Truhlar, Jiali Gao

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

A subject of great practical importance that has not received much attention is the question of the sensitivity of molecular dynamics simulations to the initial X-ray structure used to set up the calculation. We have found two cases in which seemingly similar structures lead to quite different results, and in this article we present a detailed analysis of these cases. The first case is acyl-CoA dehydrogenase, and the chief difference of the two structures is attributed to a slight shift in a backbone carbonyl that causes a key residue (the proton-abstracting base) to be in a bad conformation for reaction. The second case is xylose isomerase, and the chief difference of the two structures appears to be the ligand sphere of a Mg2+ metal cofactor that plays an active role in catalysis.

Original languageEnglish (US)
Pages (from-to)2341-2354
Number of pages14
JournalProtein Science
Volume13
Issue number9
DOIs
StatePublished - Sep 2004

Keywords

  • Combined quantum mechanics/molecular mechanics
  • Molecular dynamics
  • Potential of mean force
  • Structure-based enzyme modeling

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