Development of Implicit Solvation Potentials for Biomolecules

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DBI 9974621, Lazaridis, Themis. CUNY City College. Development of implicit solvation potentials for biomolecules.Project SummaryThe interaction of biological macromolecules with solvent is crucial to their structure and function and needs to be taken into account in computer modeling studies. Until now, this has been accomplished primarily by simulating the biomolecule along with a large number of water molecules. This approach (explicit solvation) has two drawbacks: it is computationally intensive and does not reveal the thermodynamic origins of the observed behavior because free energies are not readily available in the simulation. A more efficient approach to this problem (implicit solvation) is to add an analytical function for the solvation free energy to the molecular mechanics force field. Such a function for proteins in water has been recently developed and added to the CHARMM force field to obtain an approximation to the effective energy of proteins in solution (EEF1). The proposed work will continue on this path by a) further testing and developing improvements to EEF1, b) extending the model to other biomolecules, such as nucleic acids, carbohydrates, lipids, metals and cofactors, c) extending the model to other solvents, such as denaturant solutions and nonpolar environments mimickingbiological membranes, and d) incorporating the effects of pH, pKa shifts, and ionic strength. The objective of this work is to develop a set of potentials that can accurate represent the various solvent environments found in living systems and in experimental in vitro studies of biomolecules. The new potentials, implemented into existing or new software, will allow the study of larger and more complex biological systems than has been possible so far.