In s ilicoDrug Design
Garyfallia I. Makrynitsa, Michail Lykouras, Georgios A. Spyroulias, Minos–Timotheos Matsoukas · Encyclopedia of Life Sciences · 2018
Abstract In the field of computational drug design, the identification and characterisation of the biological target of interest is a major step. Despite the growing number of such resolved protein structures every year, there are still many drug targets, especially membrane proteins, for which structural determination is very difficult. In these cases, experimental knowledge on already determined bioactive molecules may be used successfully for computational ligand‐based drug‐design methods. However, for the past three decades, most drug discovery efforts have been driven by the structure of the target biomolecule. Advances in structural biology methods have provided structural information of many molecules, giving rise to the structure‐based drug‐design process as a powerful tool for drug discovery in research academia and pharmaceutical industry. Both fields in thein silicodrug‐design field are commonly used, each one depending on background experimental information and relevant computational methodologies. Key Concepts The main computer‐aided drug‐design approaches are either ligand or structure based. Main ligand‐based methods for identifying bioactive compounds are chemical similarity, pharmacophore mapping and QSAR. Advances in structural biology methodologies have greatly assisted structure‐based drug design. Structure‐based methods in computational drug design are mostly molecular docking, molecular dynamics, fragment‐based drug‐design and pharmacophore modelling. Docking and pharmacophore methodologies are most commonly used for virtual screening in drug design.