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 language | English (US) |
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Pages (from-to) | 2341-2354 |
Number of pages | 14 |
Journal | Protein Science |
Volume | 13 |
Issue number | 9 |
DOIs | |
State | Published - Sep 2004 |
Keywords
- Combined quantum mechanics/molecular mechanics
- Molecular dynamics
- Potential of mean force
- Structure-based enzyme modeling