Computational Approaches for Drug Discovery

Abstract Cellular proteins are the mediators of multiple organism functions being involved in physiological mechanisms and disease. By discovering lead compounds that affect the function of target proteins, the target diseases or physiological mechanisms can be modulated. Based on knowledge of the ligand–receptor interaction, the chemical structures of leads can be modified to improve efficacy, selectivity and reduce side effects. One rational drug design technology, which enables drug discovery based on knowledge of target structures, functional properties and mechanisms, is computer‐aided drug design (CADD). The application of CADD can be cost‐effective using experiments to compare predicted and actual drug activity, the results from which can used iteratively to improve compound properties. The two major CADD‐based approaches are structure‐based drug design, where protein structures are required, and ligand‐based drug design, where ligand and ligand activities can be used to design compounds interacting with the protein structure. Approaches in structure‐based drug design include docking, de novo design, fragment‐based drug discovery and structure‐based pharmacophore modeling. Approaches in ligand‐based drug design include quantitative structure–affinity relationship and pharmacophore modeling based on ligand properties. Based on whether the structure of the receptor and its interaction with the ligand are known, different design strategies can...
Source: Drug Development Research - Category: Drugs & Pharmacology Authors: Tags: Research Overview Source Type: research