OptZyme: computational enzyme redesign using transition state analogues.

ABSTRACT: OptZyme is a new computational procedure for designing improved enzymatic activity (i.e., kcat or kcat/KM) with a novel substrate. The key concept is to use transition state analogue compounds, which are known for many reactions, as proxies for the typically unknown transition state structures. Mutations that minimize the interaction energy of the enzyme with its transition state analogue, rather than with its substrate, are identified that lower the transition state formation energy barrier. Using Escherichia coli β-glucuronidase as a benchmark system, we confirm that KM correlates (R(2) = 0.960) with the computed interaction energy between the enzyme and the para-nitrophenyl- β, D-glucuronide substrate, kcat/KM correlates (R(2) = 0.864) with the interaction energy of the transition state

SUBMITTER: Grisewood MJ 

PROVIDER: S-EPMC3792102 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature