From laptop to benchtop to bedside:Structure-based drug design on protein targets

Lu Chen, John K. Morrow, Hoang T. Tran, Sharangdhar S. Phatak, Lei Du-Cuny, Shuxing Zhang

Research output: Contribution to journalReview articlepeer-review

70 Scopus citations

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 protein-ligand 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.

Original languageEnglish (US)
Pages (from-to)1217-1239
Number of pages23
JournalCurrent pharmaceutical design
Volume18
Issue number9
DOIs
StatePublished - Mar 2012

Keywords

  • De novo design
  • Flexible docking
  • Focused library design
  • High-throughput virtual screening
  • Pharmacophore
  • Polypharmacology
  • Protein modeling
  • Protein-protein interaction
  • Structure-based drug design

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

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