Exploring the Electronic Structure of Knotted Proteins: The Case of Two Ornithine Transcarbamylase Family

Abstract

Geometrical knots are rare structural arrangements in proteins in which the polypeptide chain ties itself into a knot, which is very intriguing due to the uncertainty of their impact on the protein properties. Presently, classical molecular dynamics is the most employed technique in the few studies found on this topic, which means that any information on how the presence of knots affects the reactivity and electronic properties of proteins is even scarcer. Thus, using the new software, PRIMoRDiA, developed by our group to explore the electronic structure of biological macromolecules, we evaluated several local quantum chemical descriptors to unveil relevant patterns potentially originating from the presence of the geometrical knot in two proteins, as a case of study. We compared several sampled structures from two enzymes that are highly similar in both tertiary structure and function, but one of them has a knot whereas the other does not. We found that the same amino-acid residues in the knot core have statistically larger values for the unknotted protein, for both hard-hard and soft-soft interaction descriptors. Additionally, we explored the variation in several reactivity and other quantum chemical properties calculated from a set of snapshot structures of whole proteins. We present a computationally feasible protocol that combines structures sampled from nanoscale molecular dynamics trajectories, semiempirical calculations of the entire protein atom set and the use of our software PRIMoRDiA to compute molecular quantum chemical descriptors. From this protocol we showed that the is possible to separate the contribution of the geometrical knot to the reactivity and other electronic structure properties.