Dynamic simulations as a complement to experimental studies of enzyme mechanisms

Dynamic simulations are a useful means of studying certain aspects of enzyme reaction mechanisms that cannot be understood easily through current experimental methods. With increases in computing power and innovations with computer hardware, more and more accurate techniques for modeling biological systems at the atomic level are under development. Here, we discuss two enzyme systems that illustrate the utility of dynamic simulations in conjunction with experimental studies. The first involves the use of X-ray crystal structures, kinetic studies, and molecular dynamics simulations in the study of the reduction of the prodrug CB1954 (5-(aziridin-1-yl)-2,4-dinitrobenzamide) by the flavoenzyme nitroreductase from Escherichia coli. The second involves the study of the mechanism of the Salmonella serovars phosphothreonine lyase SpvC using X-ray crystal structures, biochemical assays, molecular dynamics simulations, and potential mean force calculations. It is only through a combination of experimental and computational techniques that a thorough atomic-level understanding of these enzyme reaction mechanisms is achieved.