Two physics-based models for pH-dependent calculations of protein solubility.

ABSTRACT: When engineering a protein for its biological function, many physicochemical properties are also optimized throughout the engineering process, and the protein's solubility is among the most important properties to consider. Here, we report two novel computational methods to calculate the pH-dependent protein solubility, and to rank the solubility of mutants. The first is an empirical method developed for fast ranking of the solubility of a large number of mutants of a protein. It takes into account electrostatic solvation energy term calculated using Generalized Born approximation, hydrophobic patches, protein charge, and charge asymmetry, as well as the changes of protein stability upon mutation. This method has been tested on over 100 mutations for 17 globular proteins, as well as on 44

SUBMITTER: Spassov VZ 

PROVIDER: S-EPMC8996476 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature