Relevance of Molecular Docking Studies in Drug Designing

Abstract

Molecular Docking is used to positioning the computer-generated 3D structure of small ligands into a receptor structure in a variety of orientations, conformations and positions. This method is useful in drug discovery and medicinal chemistry providing insights into molecular recognition. Docking has become an integral part of Computer-Aided Drug Design and Discovery (CADDD). Traditional docking methods suffer from limitations of semi-flexible or static treatment of targets and ligand. Over the last decade, advances in the field of computational, proteomics and genomics have also led to the development of different docking methods which incorporate protein-ligand flexibility and their different binding conformations. Receptor flexibility accounts for more accurate binding pose predictions and a more rational depiction of protein binding interactions with the ligand. Protein flexibility has been included by generating protein ensembles or by dynamic docking methods. Dynamic docking considers solvation, entropic effects and also fully explores the drug-receptor binding and recognition from both energetic and mechanistic point of view. Though in the fast-paced drug discovery program, dynamic docking is computationally expensive but is being progressively used for screening of large compound libraries to identify the potential drugs. In this review, a quick introduction is presented to the available docking methods and their application and limitations in drug discovery.