Novel, provable algorithms for efficient ensemble-based computational protein design and their application to the redesign of the c-Raf-RBD:KRas protein-protein interface.

ABSTRACT: The K* algorithm provably approximates partition functions for a set of states (e.g., protein, ligand, and protein-ligand complex) to a user-specified accuracy ε. Often, reaching an ε-approximation for a particular set of partition functions takes a prohibitive amount of time and space. To alleviate some of this cost, we introduce two new algorithms into the osprey suite for protein design: fries, a Fast Removal of Inadequately Energied Sequences, and EWAK*, an Energy Window Approximation to K*. fries pre-processes the sequence space to limit a design to only the most stable, energetically favorable sequence possibilities. EWAK* then takes this pruned sequence space as input and, using a user-specified energy window, calculates K* scores using the lowest energy conformations. We expect fri

SUBMITTER: Lowegard AU 

PROVIDER: S-EPMC7329130 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature