Modern drug discovery for inflammatory bowel disease: The role of computational methods

Abstract

Inflammatory bowel diseases (IBDs) comprising ulcerative colitis, Crohn’s disease and microscopic colitis are characterized by chronic inflammation of the gastrointestinal tract. IBD has spread around the world and is becoming more prevalent at an alarming rate in developing countries whose societies have become more westernized. Cell therapy, intestinal microecology, apheresis therapy, exosome therapy and small molecules are emerging therapeutic options for IBD. Currently, it is thought that low-molecular-mass substances with good oral bio-availability and the ability to permeate the cell membrane to regulate the action of elements of the inflammatory signaling pathway are effective therapeutic options for the treatment of IBD. Several small molecule inhibitors are being developed as a promising alternative for IBD therapy. The use of highly efficient and time-saving techniques, such as computational methods, is still a viable option for the development of these small molecule drugs. The computer-aided ( in silico ) discovery approach is one drug development technique that has mostly proven efficacy. Computational approaches when combined with traditional drug development methodology dramatically boost the likelihood of drug discovery in a sustainable and cost-effective manner. This review focuses on the modern drug discovery approaches for the design of novel IBD drugs with an emphasis on the role of computational methods. Some computational approaches to IBD genomic studies, target identification, and virtual screening for the discovery of new drugs and in the repurposing of existing drugs are discussed.

Benchmarking different docking protocols for predicting the binding poses of ligands complexed with cyclooxygenase enzymes and screening chemical libraries

“…Nowadays, computational studies such as protein structure modeling, molecular mechanics calculations, molecular dynamics simulations, QSAR analyses, pharmacophore modeling, and molecular docking are extensively practiced at different steps of drug design and discovery pipeline including target identification and optimization, target structure prediction, virtual library generation and screening, lead identification and optimization and activity prediction. [46][47][48][49][50][51] One of the widely used computational methods which is applied at different stages of drug discovery and development is molecular docking. Molecular docking is a computational method to predict binding conformation and orientation of a ligand (usually a small molecule) when interacts with its receptor (protein or DNA).…”

Approaches, Strategies and Procedures for Identifying Anti-Inflammatory Drug Lead Molecules from Natural Products

“…The initial phases of discovery and preclinical efforts contribute to over 43% of expenses [ 63 ]. To address this challenge, the integration of extremely effective and time-efficient strategies, such as computer-aided drug discovery [ 64 ], when merged with traditional drug development techniques, has significantly boosted the probability of drug discovery from NPs [ 65 ].…”

Pharmaceutical Potential of Remedial Plants and Helminths for Treating Inflammatory Bowel Disease

“…For instance, GC-MSidentified bioactive ingredients and molecular docking against key targets revealed 3,5dehydro-6-methoxy, ethyl iso-allocholate cholest-22-ene-21-ol, alpha-cadinol, and pivalate of Phyllanthus nivosus as promising compounds for UC drug development [218]. Computational methods, particularly in silico discovery, enhance traditional drug development, ensuring sustainable and cost-effective drug discovery with increased efficacy [219]. Modern techniques like pharmacophore modeling are also crucial for virtual screening, utilizing advanced compound databases and computing power to find small molecules of lead compounds [17].…”