Dynamical theory of activated processes in globular proteins.

Scott H. Northrup; Michael R. Pear; C Y Lee; J. Andrew McCammon; Martin Karplus

doi:10.1073/pnas.79.13.4035

Abstract

A method is described for calculating the reaction rate in globular proteins of activated processes such as ligand binding or enzymatic catalysis. The method is based on the determination of the probability that the system is in the transition state and of the magnitude of the reactive flux for transition-state systems. An "umbrella sampling" simulation procedure is outlined for evaluating the transition-state probability. The reactive flux is obtained from an approach described previously for calculating the dynamics of transition-state trajectories. An application to the rotational isomerization of an aromatic ring in the bovine pancreatic trypsin inhibitor is presented. The results demonstrate the feasibility of calculating rate constants for reactions in proteins and point to the importance of solvent effects for reactions that occur near the protein surface.

Keywords

Globular proteinTransition state theoryReaction rate constantChemistryChemical physicsTransition stateGlobular clusterIsomerizationComputational chemistryCatalysisStatistical physicsPhysicsKineticsCrystallographyClassical mechanicsOrganic chemistryQuantum mechanics

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Publication Info

Year: 1982
Type: article
Volume: 79
Issue: 13
Pages: 4035-4039
Citations: 193
Access: Closed

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APA Style

                            
                                
                                    Scott H. Northrup, 
                                
                                    Michael R. Pear, 
                                
                                    C Y Lee
                                
                                et al.
                            
                            (1982). 
                            Dynamical theory of activated processes in globular proteins.. 
                            Proceedings of the National Academy of Sciences
                            , 79
                            (13)
                            , 4035-4039.
                            https://doi.org/10.1073/pnas.79.13.4035
                        

Identifiers

DOI: 10.1073/pnas.79.13.4035