Redesigning methionyl-tRNA synthetase for β-methionine activity with adaptive landscape flattening and experiments.

ABSTRACT: Amino acids (AAs) with a noncanonical backbone would be a valuable tool for protein engineering, enabling new structural motifs and building blocks. To incorporate them into an expanded genetic code, the first, key step is to obtain an appropriate aminoacyl-tRNA synthetase. Currently, directed evolution is not available to optimize AAs with noncanonical backbones, since an appropriate selective pressure has not been discovered. Computational protein design (CPD) is an alternative. We used a new CPD method to redesign MetRS and increase its activity towards β-Met, which has an extra backbone methylene. The new method considered a few active site positions for design and used a Monte Carlo exploration of the corresponding sequence space. During the exploration, a bias energy was adaptively l

SUBMITTER: Opuu V 

PROVIDER: S-EPMC10451022 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature