Homology Modelling: A Computational Tool in Drug Design and Discovery

Abstract

A drug takes many years to develop and reach the market using the conventional drug discovery procedure. Computer-aided drug design (CADD) is an emerging technology that accelerates the process of drug discovery and minimizes the total expenditure associated with labour and resources. In the current scenario, the computational aided drug design (CADD) techniques play a significant role in the design and development of lead molecules for the treatment of various lethal pathological conditions. The prediction of the tertiary structure of a protein is a big concern in drug design and discovery. A typical drug discovery procedure starts with the tertiary structure of a protein. At present, a total of 184,407 protein structures are available in the protein data bank, which are determinedusing experimental methods. However, the procedures are difficult and time-consuming. A more advanced technique has been developed for the prediction of the 3D structure of a protein using a computational method. This technique has played a vital role in drug discovery. It has not only facilitated but also hastened the process of drug discovery. The method is named homology modeling since it involves the building of a protein model based on its homology to similar evolutionary proteins. The method is based on the fact that evolutionary related proteins have similar structures. In homology modelling, the 3D structure of a protein is derived from its primary sequence based on its similarity to the existing protein templates. There are many computational tools for homology modelling such as Modeller, Swiss model, Composer, 3D-JIGSAW, etc. The proposed book chapter will cover the introduction to homology modelling, step-by-step guide to building a protein model, various challenges and how to refine and validate the model, different algorithms related to sequence alignment, similarity search, and the applications of homology modelling in drug design and discovery. The chapter would be very fruitful to the readers to get insights into protein modelling, which will facilitate their research activities. It will be of great application in various disciplines,such as bioinformatics, physics, structural biology, and molecular biology. The content of the chapter will cover various research papers, review papers, and corresponding reference books.