Binding and docking interactions of NO, CO and O₂in heme proteins as probed by density functional theory.

Vangelis Daskalakis,Constantinos Varotsis

doi:10.3390/ijms10094137

Abstract

Dynamics and reactivity in heme proteins include direct and indirect interactions of the ligands/substrates like CO, NO and O2 with the environment. Direct electrostatic interactions result from amino acid side chains in the inner cavities and/or metal coordination in the active site, whereas indirect interactions result by ligands in the same coordination sphere. Interactions play a crucial role in stabilizing transition states in catalysis or altering ligation chemistry. We have probed, by Density Functional Theory (DFT), the perturbation degree in the stretching vibrational frequencies of CO, NO and O2 molecules in the presence of electrostatic interactions or hydrogen bonds, under conditions simulating the inner cavities. Moreover, we have studied the vibrational characteristics of the heme bound form of the CO and NO ligands by altering the chemistry of the proximal to the heme ligand. CO, NO and O2 molecules are highly polarizable exerting vibrational shifts up to 80, 200 and 120 cm−1, respectively, compared to the non-interacting ligand. The importance of Density Functional Theory (DFT) methodology in the investigation of the heme-ligand-protein interactions is also addressed.

Highlights

We can divide NO, CO and O2 ligand molecules interactions inside a protein into two different groups
Intracavity dynamics play a major role in the function of protein and enzymes [51,61,62,63,64,65,66,67,68]
Ligand molecules are directed into the active site or internal cavities of a protein and/or though channels

Summary

Introduction

We can divide NO, CO and O2 ligand molecules interactions inside a protein into two different groups. The second one, called the bound interactions, deals with the bound forms of the ligand molecules and either the related changes in the coordination sphere of the associated metal or other interactions that influence their binding energies and chemistry. As for the latter we will focus on the proximal interactions in the heme bound forms of the ligand molecules and in the deprotonation/protonation events in the coordination sphere of the CuB metal of Cytochrome c. Several theoretical studies [1,2,3,4,5,6,7,8,9,10,11] primarily based on Density Functional

Methods

Results

Conclusion