Optimizing ligand charges for maximum binding affinity. A solvated interaction energy approach
We show that for a given binding site and a given spatial arrangement of atoms in a ligand, there exists an optimal set of partial charges at the atom centers that will optimize the net electrostatic binding free energy of the ligand. This optimal value can be calculated quite readily from a simple quadratic polynomial with coefficients derivable from a few continuum dielectric solvation calculations using a boundary element (BEM) solution of the
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