Computational Solvent Mapping

Computational solvent mapping of proteins employs molecular probes - small molecules or functional groups - to identify the most favorable binding positions. While X-ray crystallography and NMR reveal that organic solvents bind to a limited number of sites on a protein, current mapping methods result in hundreds of energy minima. We have developed mapping algorithms that move the molecular probes around the protein surface, find favorable positions using empirical free energy functions, cluster the conformations, and rank the clusters on the basis of the average free energy. The mapping procedures reproduce the available experimental solvent mapping results, eliminating the problem of spurious local minima associated with previous computational methods. Mapping both the bound and apo forms of several proteins shows that the approach is generally much less sensitive to variations in the structure of the protein than docking methods, and it is also remarkably robust against changes in the algorithm and energy parameters.

Dennis S, Kortvelyesi T, and Vajda S. Computational mapping identifies the binding sites of organic solvents on proteins. Proc. Natl. Acad. Sci. USA. 99(7): 4290-4295, 2002. PDF

Kortvelyesi, T., Dennis, S., Silberstein, M., Brown III, L., and Vajda, S. Algorithms for computational solvent mapping of proteins. Proteins, 51: 340-351, 2003. PDF

Kortvelyesi, T., Silberstein, M, Dennis, S. and Vajda, S. Improved mapping of protein binding sites. Journal of Computer-Aided Molecular Design, in press.