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 language | English (US) |
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Pages (from-to) | 1217-1239 |
Number of pages | 23 |
Journal | Current pharmaceutical design |
Volume | 18 |
Issue number | 9 |
DOIs | |
State | Published - 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