Prediction of protein solubility from calculation of transfer free energy.

ABSTRACT: Solubility plays a major role in protein purification, and has serious implications in many diseases. We studied the effects of pH and mutations on protein solubility by calculating the transfer free energy from the condensed phase to the solution phase. The condensed phase was modeled as an implicit solvent, with a dielectric constant lower than that of water. To account for the effects of pH, the protonation states of titratable side chains were sampled by running constant-pH molecular dynamics simulations. Conformations were then selected for calculations of the electrostatic solvation energy: once for the condensed phase, and once for the solution phase. The average transfer free energy from the condensed phase to the solution phase was found to predict reasonably well the variations i

SUBMITTER: Tjong H 

PROVIDER: S-EPMC2527251 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature