Abstract
Analytic and numerical methods now allow optimization of the electrostatic contribution to the free energy of association of two molecules in solution. Using a continuum electrostatic approximation based on the linearized Poisson-Boltzmann equation, the electrostatic free energy of rigid bimolecular association becomes a quadratic function of the reactant-charge distributions. By optimizing the charge distribution of one reactant, we find that the electrostatic free energy can be minimized, and made favorable in many cases. Furthermore, a rigorous method for visualizing the extent of electrostatic complementarity between two molecules has been developed. In this paper we review the framework and progress of charge optimization and discuss some of the implications emerging to date.
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Kangas, E., Tidor, B. (2000). Electrostatic Optimization in Ligand Complementarity and Design. In: Floudas, C.A., Pardalos, P.M. (eds) Optimization in Computational Chemistry and Molecular Biology. Nonconvex Optimization and Its Applications, vol 40. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-3218-4_13
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DOI: https://doi.org/10.1007/978-1-4757-3218-4_13
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