Modern Approaches to Analysis of Protein–Ligand Interactions

Resumo

Abstract—The capabilities of computer analysis of the conformational properties of proteins and the nature of their interactions with ligands are rapidly growing due to the development of molecular modeling methods and advances in computer technology. Despite this, the existing theoretical methods are still far from ideal and their predictions require experimental verification. Therefore, accurate experimental methods for measuring the parameters of interaction between proteins and small molecules are in high demand to address both fundamental and applied issues, such as the study of intracellular processes and the creation of new drugs. In this review, we consider three well-proven modern biophysical techniques for the determination of the affinity, stoichiometry, and energy of the interaction of proteins with ligands: isothermal titration calorimetry, microscale thermophoresis, and surface plasmon resonance. Particular attention is paid to the development of the technical capabilities of these methods in recent years, the intricacies of their practical use, and illustrations of their application to solve specific biophysical problems in pharmacology.