From Laptop to Benchtop to Bedside: Structure-based Drug Design on Protein Targets

Title: From Laptop to Benchtop to Bedside: Structure-based Drug Design on Protein Targets

Volume: 18 Issue: 9

Author(s): Lu Chen, John K. Morrow, Hoang T. Tran, Sharangdhar S. Phatak, Lei Du-Cuny and Shuxing Zhang

Affiliation:

Keywords: Structure-based drug design, protein modeling, focused library design, pharmacophore, flexible docking, high-throughput virtual screening, de novo design, protein-protein interaction, polypharmacology

Abstract: As an important aspect of computer-aided drug design, structure-based drug design brought a new horizon to pharmaceutical development. This in silico method permeates all aspects of drug discovery today, including lead identification, lead optimization, ADMET prediction and drug repurposing. Structure-based drug design has resulted in fruitful successes drug discovery targeting proteinligand and protein-protein interactions. Meanwhile, challenges, noted by low accuracy and combinatoric issues, may also cause failures. In this review, state-of-the-art techniques for protein modeling (e.g. structure prediction, modeling protein flexibility, etc.), hit identification/ optimization (e.g. molecular docking, focused library design, fragment-based design, molecular dynamic, etc.), and polypharmacology design will be discussed. We will explore how structure-based techniques can facilitate the drug discovery process and interplay with other experimental approaches.

Cite this article as:

Chen Lu, K. Morrow John, T. Tran Hoang, S. Phatak Sharangdhar, Du-Cuny Lei and Zhang Shuxing, From Laptop to Benchtop to Bedside: Structure-based Drug Design on Protein Targets, Current Pharmaceutical Design 2012; 18 (9) . https://dx.doi.org/10.2174/138161212799436386