Correlation between Interaction Energy by Fragment Molecular Orbital Method and Enthalpy Change

Abstract

Fragment molecular orbital (FMO) method has recently been used to analyze interactions between proteins and inhibitors for the purpose of drug discovery research. Unlike methods that use force field such as docking simulations, FMO method considered electrons. Therefore, it is characterized by the ability to analyze interactions involving electron correlation such as dispersion force. Furthermore, if a strong correlation can be obtained between the sum of inter-fragment interaction energy (IFIE-sum) and the enthalpy change between the protein and the inhibitor, we have also devised a method to predict free energy changes only by obtaining fragment interaction energies. As part of this research, we investigated the correlation between IFIE-sum and the enthalpy change in HIV protease inhibitors, and obtained a good correlation by appropriately classifying the target structures.