Modeling Protein Properties using pH-dependent Conformational Sampling
John Gunn (Chemical Computing Group ULC.)
Abstract: Proteins present particular challenges for property calculations due to their conformational flexibility in solution and the sensitivity of the structure to environmental parameters such as buffer strength and pH. We present a novel method for calculating thermodynamically averaged properties using a conformational ensemble which correctly takes into account the variability of both the structure and the charge state (protonation) of the protein.
The validity of this approach will be demonstrated using various benchmark calculations with experimental reference data, and additional applications will be shown with an emphasis toward modeling developability criteria for therapeutic antibodies.