Using protein-ligand docking to assess the chemical tractability of inhibiting a protein target

被引：0
作者：
Richard A. Ward
机构：
[1] Cancer & Infection Discovery,
[2] AstraZeneca,undefined
来源：
Journal of Molecular Modeling | 2010年 / 16卷
关键词：
Druggability; Ligandability; Protein-ligand docking;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
Assessing the difficulty of inhibiting a specific protein by a small molecule can be highly valuable in risk-assessment and prioritization of a new target. In particular, when the disease linkage for a number of targets is broadly similar, being able to identify the most tractable can have a significant impact on informing target selection. With an increasing focus against new and novel protein classes, being able to assess the most likely targets to yield lead-like chemical start points can guide the selection and the lead-generation strategy implemented. This study exploits protein-ligand docking studies on published protein x-ray crystal structures to provide guidance on the feasibility of identifying small molecule inhibitors against a range of targets.
引用
收藏
页码：1833 / 1843
页数：10
相关论文
共 123 条
  • [1] Brown D(2003)Rediscovering the sweet spot in drug discovery Drug Discov Today 8 1067-1077
  • [2] Superti-Furga G(2005)Druggability indices for protein targets derived from NMR-based screening data J Med Chem 48 2518-2525
  • [3] Hajduk PJ(2002)The druggable genome Nat Rev Drug Disc 1 727-730
  • [4] Huth JR(2005)Predicting protein druggability Drug Discov Today 10 1675-1682
  • [5] Fesik SW(2006)Predicting protein interaction sites: binding hot-spots in protein–protein and protein–ligand interfaces Bioinformatics 22 1335-1342
  • [6] Hopkins AL(2009)Predicting druggable binding sites at the protein–protein interface Drug Discov Today 14 155-161
  • [7] Groom CR(2007)Structure-based maximal affinity model predicts small-molecule druggability Nat Biotechnol 25 71-75
  • [8] Hajduk PJ(2001)High-throughput structural proteomics using x-rays Trends Biotechnol 19 67-71
  • [9] Huth JR(1958)Application of a theory of enzyme specificity to protein synthesis Proc Natl Acad Sci 44 98-104
  • [10] Tse C(2006)Between a rock and a hard place? Nat Chem Biol 2 112-118
12345678910