Approaching protein design with multisite λ dynamics: Accurate and scalable mutational folding free energies in T4 lysozyme.

ABSTRACT: The estimation of changes in free energy upon mutation is central to the problem of protein design. Modern protein design methods have had remarkable success over a wide range of design targets, but are reaching their limits in ligand binding and enzyme design due to insufficient accuracy in mutational free energies. Alchemical free energy calculations have the potential to supplement modern design methods through more accurate molecular dynamics based prediction of free energy changes, but suffer from high computational cost. Multisite λ dynamics (MSλD) is a particularly efficient and scalable free energy method with potential to explore combinatorially large sequence spaces inaccessible with other free energy methods. This work aims to quantify the accuracy of MSλD and demonstrate its sc

SUBMITTER: Hayes RL 

PROVIDER: S-EPMC6225981 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature