I want to know the use of solute dielectric constant in MM-PBSA calculations of the protein-ligand complex and what is the criteria of selecting pdie value for a particular system. Though the default value is 2, but in literature, I have seen people are using a range of pdie value from 1 to 20 depending on the type of system (neutral or charged). Is there any specific reason for the selection of particular pdie value while performing the calculations?
Pdie is featured in the Poisson-Boltzmann equation, thus the modification of it will influence the polar term calculated by MM/PBSA method.
Low pdie value (1 or 2) is shown to be more suitable for protein with hydrophobic binding site, while higher values are for binding site with highly charged residues. Correct selection will lead to at least improved correlation coefficients, sometimes also improved absolute binding free energy prediction (although it is not really expected in MM/PBSA to calculate absolute free energy value).
There is no golden bullet that can be chosen in advance. One can perform validation by inspecting the characteristic of the binding site and tune the pdie with two optional values, for example. The result from the validation can be used as a reference for particular protein of interest.
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