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Sensitivity of molecular dynamics simulations to the choice of the X‐ray structure used to model an enzymatic reaction
Author(s) -
GarciaViloca Mireia,
Poulsen Tina D.,
Truhlar Donald G.,
Gao Jiali
Publication year - 2004
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1110/ps.03504104
Subject(s) - chemistry , cofactor , molecular dynamics , ligand (biochemistry) , enzyme catalysis , stereochemistry , active site , catalysis , isomerase , computational chemistry , enzyme , organic chemistry , receptor , biochemistry
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 Mg 2+ metal cofactor that plays an active role in catalysis.