… focuses on the experimental determination of the effect of protonation on the binding of small molecules to proteins. Based on potentiometric, ITC and NMR experiments, we can macroscopically assess the relationships between protein-bound protonation states and those observed in aqueous solution. These experiments inform our computational efforts, which analyze these effects at an atomic level, and will lead to improvements in theoretical and computational models.
As part of a continuing iterative cycle, our computational studies suggest new systems for experimental determination or re-testing based on mismatches between theory and experiment. This interplay between wet lab and dry lab allows us to obtain a full understanding of a very often overlooked component of molecular recognition: Protonation!