Transition path sampling is a well-known technique that generates reactive paths ensembles. Due to the atomic detail of these reactive paths, information about chemical mechanisms can be obtained. We present here a comparative study of Bacillus stearothermophilus and human heart homologues of lactate dehydrogenase (LDH). A comparison of the transition path ensemble of both enzymes revealed that small differences in the active site reverses the order of the particle transfer of the chemical step. Whereas the hydride transfer preceded the proton transfer in the human heart LDH, the order is reversed in the Bacillus stearothermophilis homologue (in the direction of pyruvate to lactate). In addition, transition state analysis revealed that the dividing region that separates reactants and products, the separatrix, is likely wider for B. stearothermophilis LDH as compared to human heart LDH. This would indicate a more variable transition process in the Bacillus enzyme.
ASJC Scopus subject areas
- Physical and Theoretical Chemistry