Automatic characterization of drug/amino acid interactions by energy decomposition analysis

Abstract

The computational study of drug/protein interactions is fundamental to understand the mode of action of drugs and design new ones. In this study, we have developed a python code aimed at characterizing the nature of drug/amino acids interactions in an accurate and automatic way. Specifically, the code is interfaced with different software packages to compute the interaction energy quantum mechanically, and obtain its different contributions, namely, Pauli repulsion, electrostatic and polarisation terms, by an energy decomposition analysis based on one-electron and two-electron deformation densities. The code was tested by investigating the nature of the interaction between the glycine amino acid and 250 drugs. An energy-structure relationship analysis reveals that the strength of the electrostatic and polarisation contributions is related with the presence of small and large size heteroatoms, respectively, in the structure of the drug.