Lu Chen, John K. Morrow, Hoang T. Tran, Sharangdhar S. Phatak, Lei Du-Cuny and Shuxing Zhang Pages 1217 - 1239 ( 23 )
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.
Structure-based drug design,protein modeling,focused library design,pharmacophore,flexible docking,high-throughput virtual screening,de novo design,protein-protein interaction,polypharmacology
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