Sensitivity of molecular dynamics simulations to the choice of the X-ray structure used to model an enzymatic reaction |
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Authors: | Garcia-Viloca Mireia Poulsen Tina D Truhlar Donald G Gao Jiali |
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Institution: | Department of Chemistry and Supercomputer Institute, University of Minnesota, Minneapolis, MN 55455, USA. |
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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. |
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Keywords: | combined quantum mechanics/molecular mechanics molecular dynamics potential of mean force structure-based enzyme modeling |
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