Density functional theory studies of MTSL nitroxide side chain conformations attached to an activation loop

TL;DR

This study uses density functional theory to analyze the conformations of MTSL nitroxide side chains attached to an activation loop, revealing low energy barriers and rotamer populations relevant for protein modeling.

Contribution

It demonstrates that the conformational landscape of MTSL attached to a protein loop can be characterized using DFT, with findings applicable to other protein systems.

Findings

Low energy barriers between conformers

X3, X4, and X5 dihedral angles are independent of previous angles

Conformational states are similar to those in alpha-helix systems

Abstract

A quantum-mechanical (QM) method rooted on density functional theory (DFT) has been employed to determine conformations of the methane-thiosulfonate spin label (MTSL) attached to a fragment extracted from the activation loop of Aurora-A kinase. The features of the calculated energy surface revealed low energy barriers between isoenergetic minima and the system could be described in a population of 76 rotamers that can be also considered for other systems since it was found that the X3, X4 and X5 do not depend on the previous two dihedral angles. Conformational states obtained were seen to comparable to those obtained in the {\alpha}-helix systems studied previously, indicating that the protein backbone does not affect the torsional profiles significantly and suggesting the possibility to use determined conformations for other protein systems for further modelling studies.