Cole DJ

Lever G

Lonsdale R

Mulholland AJ

Payne MC

Ranaghan KE

Skylaris C-K

Wales DJ

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

Newcastle University E-Prints

Large-Scale Density Functional Theory Transition State Searching in Enzymes

Large-Scale Density Functional Theory Transition State Searching in Enzymes

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