Multi-state design of flexible proteins predicts sequences optimal for conformational change.

ABSTRACT: Computational protein design of an ensemble of conformations for one protein-i.e., multi-state design-determines the side chain identity by optimizing the energetic contributions of that side chain in each of the backbone conformations. Sampling the resulting large sequence-structure search space limits the number of conformations and the size of proteins in multi-state design algorithms. Here, we demonstrated that the REstrained CONvergence (RECON) algorithm can simultaneously evaluate the sequence of large proteins that undergo substantial conformational changes. Simultaneous optimization of side chain conformations across all conformations increased sequence conservation when compared to single-state designs in all cases. More importantly, the sequence space sampled by RECON MSD resembl

SUBMITTER: Sauer MF 

PROVIDER: S-EPMC7032724 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature