Quantum mechanics analysis of field effects on the main chain atoms of amino acids

Abstract

Electronic factors that modulate the folding and functional activity of proteins are poorly understood. Field effects, in particular, appear to play an important role in enzyme catalysis and stabilization of drug binding. In this study, quantum mechanics (QM) calculations were used to analyze the field effects of two external molecules, water and amino acids, on the electron distributions in main chain atoms of amino acids. When water was complexed with the 20 amino acids in a hydrogen bond, there were significant changes in the electron densities at all main chain atoms. Amino acids complexed with a probe molecule (glycine) produced consistent changes in electron densities when positioned 3.5-6 angstroms from the probe. As expected, field effects revealed by QM analysis weakened as a function of distance. N and Calpha atoms were especially sensitive to the field effects of nearby amino acids. Electron density at these two atoms is a useful indicator of secondary conformation, which suggests that structural preferences of amino acids may be modulated by field effects. Further investigation of this system may enhance our understanding of how electronic effects on amino acids influence the folding of proteins and determine the properties their active sites.