Harnessing conformational dynamics in enzyme catalysis to achieve nature-like catalytic efficiencies: the shortest path map tool for computational enzyme redesign.

ABSTRACT: Enzymes exhibit diverse conformations, as represented in the free energy landscape (FEL). Such conformational diversity provides enzymes with the ability to evolve towards novel functions. The challenge lies in identifying mutations that enhance specific conformational changes, especially if located in distal sites from the active site cavity. The shortest path map (SPM) method, which we developed to address this challenge, constructs a graph based on the distances and correlated motions of residues observed in nanosecond timescale molecular dynamics (MD) simulations. We recently introduced a template based AlphaFold2 (tAF2) approach coupled with 10 nanosecond MD simulations to quickly estimate the conformational landscape of enzymes and assess how the FEL is shifted after mutation. In thi

SUBMITTER: Duran C 

PROVIDER: S-EPMC11389851 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature