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.

Dasatinib–SIK2 Binding Elucidated by Homology Modeling, Molecular Docking, and Dynamics Simulations

“… 54 , 55 Molecular docking creates a static image of the drug–target complex and is also used in drug design. 56 − 64 Molecular dynamics (MD) helps elucidate the interactions in drug binding. 65 − 73 …”

LC-MS/MS-Based Quantitative Proteomics Analysis of Different Stages of Non-Small-Cell Lung Cancer

“…Thus, the associated protein content is increased [ 26 , 27 ] relative to normal cells. Elongation factor 1-alpha 2 has been reported in the literature as a potential marker for cancer [ 17 ]. The proteasome subunit alpha type is significantly increased in all cancers, consistent with literature reports [ 17 , 27 , 28 ].…”

“…Elongation factor 1-alpha 2 has been reported in the literature as a potential marker for cancer [ 17 ]. The proteasome subunit alpha type is significantly increased in all cancers, consistent with literature reports [ 17 , 27 , 28 ]. Protein ubiquitination and subsequent proteolysis and degradation by the proteasome are important mechanisms in the cell cycle, cell growth and differentiation, gene transcription, signal transduction, and apoptosis [ 29 ].…”

“…Proteomics is widely used in basic and clinical medical research [ 7 ] for the identification of biomarkers [ 8 , 9 ], posttranslational protein modifications [ 10 ], and the regulation of signaling pathways [ 11 ]. Proteomics research of lung cancer has focused on the classification of lung cancer [ 12 ], the correlation between protein and gene expressions [ 13 , 14 ], identification of new molecular targets [ 15 , 16 ], and the development of new drugs [ 17 , 18 ]. Early diagnostic markers for lung cancer [ 19 , 20 ] have been identified, but the markers still lack accuracy and sensitivity.…”

Molecular Engineering of Curcumin, an Active Constituent of Curcuma longa L. (Turmeric) of the Family Zingiberaceae with Improved Antiproliferative Activity

“…In silico molecular docking analysis was carried out against EGFR through the Schrodinger’s software. As molecular docking is now an integral part of computer-aided drug design (CADD), in which ligands with computed generated 3D structures are positioned into a receptor or biological target in a variety of orientations, conformations, and positions [ 37 ], it has numerous uses and applications in drug discovery, including structure–activity studies, lead optimization, and virtual screening to find potential leads [ 38 ]. Indeed, molecular docking has been used for more than three decades, and it has resulted in the discovery and development of a large number of new drugs [ 39 ].…”