Biomol Ther.  2017 Jan;25(1):57-68. 10.4062/biomolther.2016.199.

Evolutionary and Comparative Genomics to Drive Rational Drug Design, with Particular Focus on Neuropeptide Seven-Transmembrane Receptors

• Furlong M
• Seong JY

• KMID: 2367619
• DOI: http://doi.org/10.4062/biomolther.2016.199

Abstract

Seven transmembrane receptors (7TMRs), also known as G protein-coupled receptors, are popular targets of drug development, particularly 7TMR systems that are activated by peptide ligands. Although many pharmaceutical drugs have been discovered via conventional bulk analysis techniques the increasing availability of structural and evolutionary data are facilitating change to rational, targeted drug design. This article discusses the appeal of neuropeptide-7TMR systems as drug targets and provides an overview of concepts in the evolution of vertebrate genomes and gene families. Subsequently, methods that use evolutionary concepts and comparative analysis techniques to aid in gene discovery, gene function identification, and novel drug design are provided along with case study examples.

Keyword

Neuropeptide; 7TMR; G protein-coupled receptor; Coevolution; Gene duplication; Whole genome duplication; Evolutionary history

MeSH Terms

Drug Design*
Gene Duplication
Genetic Association Studies
Genome
Genomics*
Humans
Ligands
Neuropeptides*
Vertebrates
Ligands
Neuropeptides