Modeling Structural Constraints on Protein Evolution via Side-Chain Conformational States.

ABSTRACT: Few models of sequence evolution incorporate parameters describing protein structure, despite its high conservation, essential functional role and increasing availability. We present a structurally aware empirical substitution model for amino acid sequence evolution in which proteins are expressed using an expanded alphabet that relays both amino acid identity and structural information. Each character specifies an amino acid as well as information about the rotamer configuration of its side-chain: the discrete geometric pattern of permitted side-chain atomic positions, as defined by the dihedral angles between covalently linked atoms. By assigning rotamer states in 251,194 protein structures and identifying 4,508,390 substitutions between closely related sequences, we generate a 55-state

SUBMITTER: Perron U 

PROVIDER: S-EPMC6736381 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature