Structural Genomics in Drug Discovery: An Overview

Abstract

Structural genomics, technology and methodology driven field has emerged in the past 20–25 years and mainly aims at coming up with as many three-dimensional structures of proteins as possible by combining experimental (X-ray crystallography and nuclear magnetic resonance) and comparative modeling methods at a minimal cost in comparison to the traditional approaches. Structure aided drug discovery which is used since long mainly focuses on a single target protein whereas structural genomics targets and investigates multiple proteins simultaneously, thus cutting down time and cost. These activities are done at specialized structural genomic centers available worldwide that help to interpret the biology of humans and pathogenic organisms in a better way leading to an increased productivity and saving time. Virtual screening methods like docking have also brought a great impact to quicken the drug discovery process. In diseases of public health concern (like tuberculosis), structural genomics helped greatly by giving important insights toward a better comprehension of the pathways associated in its pathogenesis and in guiding drug discovery. Several newer targets such as Scaff10-8, MS2734 (6), and GSK-J4 were developed showcasing their beneficial effects in a wide variety of disorders including diabetes insipidus, Parkinson's disease, and autoimmune diseases, respectively. Furthermore, these programs guide to understand the root cause and the mechanism associated with various human diseases and their pathogens. This review tries to look into the high throughput methods of structure determination, the newer targets developed in the past few years and the benefits offered that can pave a way for faster and efficient drug discovery.