Applications of Current Proteomics Techniques in Modern Drug Design

Cheng-Cheng      Zhang; Juergen      Kast

Abstract

Proteins are currently the major drug targets and thus play a critical role in the process of modern drug design. This typically involves construction of drug compounds based on the structure of a drug target, validation for therapeutic efficacy of the drug compounds, evaluation of drug toxicity, and finally, clinical trial. Proteomics, defined as the comprehensive analysis of the proteins that are expressed in cells or tissues, can be employed at different stages of this process. Comparative proteomics can distinguish subtle changes in protein abundance at a depth of several thousand proteins at different conditions i.e. normal vs disease, to facilitate drug target identification. Also, chemical proteomics can be used to determine drug-target interactions and systematically analyze drug specificity and selectivity. Moreover, phosphoproteomics can be employed to monitor changes in phosphorylation events to characterize drug actions on cell signaling pathways. Similarly, functional proteomics can be utilized to investigate protein-protein and protein-ligand interactions for the clarification of the mechanism of drug action, identification of disease-related sub-networks and novel drug targets. Furthermore, quantitative proteomics can be used to characterize long-term drug effects on protein expression. In addition, computational approaches have emerged to convert complex proteomic data into sophisticated computer models of cellular protein networks. In this review, we will provide an overview of these state-of-the-art proteomics techniques, describe their underlying experimental concepts and compare them to each other, and discuss existing and future applications in the art of drug design and development.

Keywords: Proteomics, mass spectrometry, drug design, drug target discovery, drug-target interaction, post-translational modifications, protein interaction networks