Calculation of vibrational shifts of nitrile probes in the active site of ketosteroid isomerase upon ligand binding.

ABSTRACT: The vibrational Stark effect provides insight into the roles of hydrogen bonding, electrostatics, and conformational motions in enzyme catalysis. In a recent application of this approach to the enzyme ketosteroid isomerase (KSI), thiocyanate probes were introduced in site-specific positions throughout the active site. This paper implements a quantum mechanical/molecular mechanical (QM/MM) approach for calculating the vibrational shifts of nitrile (CN) probes in proteins. This methodology is shown to reproduce the experimentally measured vibrational shifts upon binding of the intermediate analogue equilinen to KSI for two different nitrile probe positions. Analysis of the molecular dynamics simulations provides atomistic insight into the roles that key residues play in determining the elect

SUBMITTER: Layfield JP 

PROVIDER: S-EPMC3547160 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature