Saturation Mutagenesis by Efficient Free-Energy Calculation.

ABSTRACT: Single-point mutations in proteins can greatly influence protein stability, binding affinity, protein function or its expression per se. Here, we present accurate and efficient predictions of the free energy of mutation of amino acids. We divided the complete mutational free energy into an uncharging step, which we approximate by a third-power fitting (TPF) approach, and an annihilation step, which we approximate using the one-step perturbation (OSP) method. As a diverse set of test systems, we computed the solvation free energy of all amino acid side chain analogues and obtained an excellent agreement with thermodynamic integration (TI) data. Moreover, we calculated mutational free energies in model tripeptides and established an efficient protocol involving a single reference state. Agai

SUBMITTER: Jandova Z 

PROVIDER: S-EPMC5813279 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature