Large-scale density functional theory transition state searching in enzymes

Greg Lever*, Daniel J. Cole, Richard Lonsdale, Kara E. Ranaghan, David J. Wales, Adrian J. Mulholland, Chris Kriton Skylaris, Mike C. Payne

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

40 Citations (Scopus)


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. (Chemical Equation Presented).

Original languageEnglish
Pages (from-to)3614-3619
Number of pages6
JournalJournal of Physical Chemistry Letters
Issue number21
Publication statusPublished - 6 Nov 2014

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