Quantum chemical descriptors based on semiempirical methods for large biomolecules

Abstract

In this Review, we reviewed the efforts to expand the applications of conceptual density functional theory reactivity descriptors and hard and soft acid and base principles for macromolecules and other strategies that focused on low-level quantum chemistry methods. Currently, recent applications are taking advantage of modifications of these descriptors using semiempirical electronic structures to explain enzymatic catalysis reactions, protein-binding processes, and structural analysis in proteins. We have explored these new solutions along with their implementations in the software PRIMoRDiA, discussing their impact on the field and its perspectives. We show the main issues in the analysis of the electronic structure of macromolecules, which are the application of the same calculation protocols used for small molecules without considering particularities in those large systems’ electronic configuration. The major result of our discussions is that the use of semiempirical methods is crucial to obtain such a type of analysis, which can provide a powerful dimension of information and be part of future low-cost predictive tools. We expect semiempirical methods continue playing an important role in the quantum chemistry evaluation of large molecules. As computational resources advance, semiempirical methods might lead us to explore the electronic structure of even larger biological macromolecular entities and sets of structures representing larger timescales.