Journal
JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN
Volume 24, Issue 11, Pages 907-916Publisher
SPRINGER
DOI: 10.1007/s10822-010-9383-z
Keywords
Protein solubility; Second osmotic virial; Calibration; Zeta potential
Ask authors/readers for more resources
A set of physicochemical properties describing a protein of known structure is employed for a calibrative approach to protein solubility. Common hydrodynamic and electrophoretic properties routinely measured in the bio-analytical laboratory such as zeta potential, dipole moment, the second osmotic virial coefficient are first estimated in silico as a function a pH and solution ionic strength starting with the protein crystal structure. The utility of these descriptors in understanding the solubility of a series of ribonuclease Sa mutants is investigated. A simple two parameter model was trained using solubility data of the wild type protein measured at a restricted number of solution pHs. Solubility estimates of the mutants demonstrate that zeta potential and dipole moment may be used to rationalize solubility trends over a wide pH range. Additionally a calibrative model based on the protein's second osmotic virial coefficient, B (22) was developed. A modified DVLO type potential along with a simplified representation of the protein allowed for efficient computation of the second viral coefficient. The standard error of prediction for both models was on the order of 0.3 log S units. These results are very encouraging and demonstrate that these models may be trained with a small number of samples and employed extrapolatively for estimating mutant solubilities.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available