Long-Range Electrostatics in Serine Proteases: Machine Learning-Driven Reaction Sampling Yields Insights for Enzyme Design.

ABSTRACT: Computational enzyme design is a promising technique for producing novel enzymes for industrial and clinical needs. A key challenge that this technique faces is to consistently achieve the desired activity. Fundamental studies of natural enzymes revealed critical contributions from second-shell - and even more distant - residues to their remarkable efficiency. In particular, such residues organize the internal electrostatic field to promote the reaction. Engineering such fields computationally proved to be a promising strategy, which, however, has some limitations. Charged residues necessarily form specific patterns of local interactions that may be exploited for structural integrity. As a result, it is impossible to probe the electrostatic field alone by substituting amino acids. We hypot

SUBMITTER: Zlobin A 

PROVIDER: S-EPMC11863386 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature