Sensitivity of molecular dynamics simulations to the choice of the X-ray structure used to model an enzymatic reaction.
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.
Garcia-Viloca
Mireia
M
Department of Chemistry and Supercomputer Institute, University of Minnesota, Minneapolis, MN 55455, USA.
Poulsen
Tina D
TD
Truhlar
Donald G
DG
Gao
Jiali
J
D042964:Acyl-CoA Dehydrogenase / Q000737:chemistry / Q000378:metabolism; D019747:Aldose-Ketose Isomerases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D002087:Butyrates / Q000737:chemistry / Q000378:metabolism; D020134:Catalytic Domain; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism; D004798:Enzymes / Q000737:chemistry* / Q000378:metabolism*; D008274:Magnesium / Q000378:metabolism; D008958:Models, Molecular; D011487:Protein Conformation; D011789:Quantum Theory; D012680:Sensitivity and Specificity; D040681:Structural Homology, Protein
D002087:Butyrates; D004791:Enzyme Inhibitors; D004798:Enzymes; C092734:threonohydroxamic acid; D042964:Acyl-CoA Dehydrogenase; D019747:Aldose-Ketose Isomerases; C023298:xylose isomerase; D008274:Magnesium