Efficient In Silico Saturation Mutagenesis of a Member of the Caspase Protease Family.

ABSTRACT: Rational-design methods have proven to be a valuable toolkit in the field of protein design. Numerical approaches such as free-energy calculations or QM/MM methods are fit to widen the understanding of a protein-sequence space but require large amounts of computational time and power. Here, we apply an efficient method for free-energy calculations that combines the one-step perturbation (OSP) with the third-power-fitting (TPF) approach. It is fit to calculate full free energies of binding from three different end states only. The nonpolar contribution to the free energies are calculated for a set of chosen amino acids from a single simulation of a judiciously chosen reference state. The electrostatic contributions, on the other hand, are predicted from simulations of the neutral and charge

SUBMITTER: Ohlknecht C 

PROVIDER: S-EPMC8023567 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature