Structure-conditioned amino-acid couplings: How contact geometry affects pairwise sequence preferences.

ABSTRACT: Relating a protein's sequence to its conformation is a central challenge for both structure prediction and sequence design. Statistical contact potentials, as well as their more descriptive versions that account for side-chain orientation and other geometric descriptors, have served as simplistic but useful means of representing second-order contributions in sequence-structure relationships. Here we ask what happens when a pairwise potential is conditioned on the fully defined geometry of interacting backbones fragments. We show that the resulting structure-conditioned coupling energies more accurately reflect pair preferences as a function of structural contexts. These structure-conditioned energies more reliably encode native sequence information and more highly correlate with experiment

SUBMITTER: Holland J 

PROVIDER: S-EPMC8927866 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature