Quantum mechanical effect in protein–ligand interaction

Abstract

Importance of the field: The development of quantum mechanics (QM) was perhaps the greatest intellectual achievement of the 20th century. Recently, QM-based methods have come to attention with the applications of studying QM effects in protein–ligand interactions. The QM-based methods give molecular-level insights into protein–ligand interactions and these can play a major role in the elucidation of the structure or reactivity of a biomolecular system.Areas covered in this review: In this review article, we present three examples to illustrate applications of QM-based methods in protein–ligand interactions. First, the QM calculation based on the density functional theory has been used to study the simplified active site model of CYP450 with an ethanol molecule. Second, a combined QM and molecular mechanical method, the generalized hybrid orbital approach, was applied to explore the identity of the fourth ligand of zinc in metalloproteins. Third, by the molecular fractionation with conjugate caps approach with full QM calculations; we obtained the interaction energies of thrombin–inhibitor complexes.What the reader will gain: Readers will gain an overview of development of QM-based methods. We summarize results from three applications of QM-based methods, each using a different method for a different system. These results show that studies of protein–ligand interactions based on QM calculations provide further descriptions of biochemical mechanisms, structures and particular interaction energies.Take home message: For the structure-based drug design, the QM-based methods will have significant applications. QM-based methods have been, and will continue to be, important tools in the study of biological systems; moreover, development of a more accurate and more efficient QM-based method is still worth waiting for.