Structural propensities of kinase family proteins from a Potts model of residue co-variation.

ABSTRACT: Understanding the conformational propensities of proteins is key to solving many problems in structural biology and biophysics. The co-variation of pairs of mutations contained in multiple sequence alignments of protein families can be used to build a Potts Hamiltonian model of the sequence patterns which accurately predicts structural contacts. This observation paves the way to develop deeper connections between evolutionary fitness landscapes of entire protein families and the corresponding free energy landscapes which determine the conformational propensities of individual proteins. Using statistical energies determined from the Potts model and an alignment of 2896 PDB structures, we predict the propensity for particular kinase family proteins to assume a "DFG-out" conformation implicat

SUBMITTER: Haldane A 

PROVIDER: S-EPMC4972195 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature