Large-Scale Density Functional Theory Transition State Searching in Enzymes

Linear-scaling quantum mechanical density functional theory calculations have been applied to study the rearrangement of chorismate to prephenate in large-scale models of the Bacillus subtilis chorismate mutase enzyme. By treating up to 2000 atoms at a consistent quantum mechanical level of theory,...

Full description

Saved in:
Bibliographic Details
Published in:The journal of physical chemistry letters 2014-11, Vol.5 (21), p.3614-3619
Main Authors: Lever, Greg, Cole, Daniel J, Lonsdale, Richard, Ranaghan, Kara E, Wales, David J, Mulholland, Adrian J, Skylaris, Chris-Kriton, Payne, Mike C
Format: Article
Language:English
Subjects:
Biophysical Chemistry and Biomolecules
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Linear-scaling quantum mechanical density functional theory calculations have been applied to study the rearrangement of chorismate to prephenate in large-scale models of the Bacillus subtilis chorismate mutase enzyme. By treating up to 2000 atoms at a consistent quantum mechanical level of theory, we obtain an unbiased, almost parameter-free description of the transition state geometry and energetics. The activation energy barrier is calculated to be lowered by 10.5 kcal mol–1 in the enzyme, compared with the equivalent reaction in water, which is in good agreement with experiment. Natural bond orbital analysis identifies a number of active site residues that are important for transition state stabilization in chorismate mutase. This benchmark study demonstrates that linear-scaling density functional theory techniques are capable of simulating entire enzymes at the ab initio quantum mechanical level of accuracy.
ISSN:1948-7185
1948-7185
DOI:10.1021/jz5018703