Computer Simulations of the Diffusion of a Substrate to an Active Site of an Enzyme

作者：Kim A. Sharp, Richard Fine, Barry H. Honig · 发表于：Science · 年份：1987 · DOI：10.1126/science.3589666 · 被引用次数：222 · 研究领域：Electrochemical Analysis and Applications、Electrochemical sensors and biosensors、Electron Spin Resonance Studies

Computer simulations of the diffusion of a substrate to an enzyme active site were performed. They included the detailed shape of the protein and an accurate description of its electrostatic potential. Application of the method to the diffusion of the superoxide anion to the protein superoxide dismutase revealed that the electric field of the enzyme enhances the association rate of the anion by a factor of 30 or more. Calculated changes in the association rate as a function of ionic strength and amino acid modification paralleled the observed behavior. Design principles of superoxide dismutase are considered with respect to insights provided by the simulations. A possible means of enhancing the enzyme turnover rate through site-directed mutagenesis is proposed.