Prediction of the Binding Affinities of PSD95 PDZ Domain in Complex with the CRIPT Peptide

Abstract

In this work, we have applied the state of art molecular dynamics simulations in combination with solvation free energy and conformational entropy calculations to predict the binding affinities of PSD95 PDZ domain in complex with the CRIPT peptide. Four diffident computational protocols were evaluated on reproducing the relative binding free energies of the wild type PDZ and its five mutants. The protocol of MM-GB/SA in combination with normal mode analysis (NMA), which has a correlation coefficient square of 0.84, apparently outperforms the others especially for the two MM-PB/SA-based protocols. Free energy decomposition was also performed in order to identify the hot spots that contribute significantly to the binding. 