Binding Affinity Prediction by Linear Response Approximation Considered Ligand Internal Energy

Abstract

It is a challenging problem to predict binding free energy between a ligand and a protein with accuracy. If this issue is addressed, precise binding affinity prediction would be considerably helpful for drug design and for understanding protein functions. A lot of methods to predict binding free energy have been reported so far. Here, we propose a new method based on the linear response approximation theory. This method is similar to the linear interaction energy (LIE) method. However, it is completely different in considering internal energy changes of ligand molecules in addition to interaction energies. In the words, it uses all potentials of a ligand molecule. Also, it requires no fitting parameters used by the LIE method. This method was applied to the adenosine deaminase inhibitors and a good correlation between calculated and experimental binding affinities has been obtained. We believe this method would be applicable to all protein systems.