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
[11]  
Burgoyne NJ(2007)An integrated approach to fragment-based lead generation:philosophy, strategy and case studies from AstraZeneca’s drug discovery programmes Curr Top Med Chem 7 1600-1629
[12]  
Jackson RM(2008)‘Rule of Three’ for fragment-based lead discovery? Drug Discov Today 8 876-877
[13]  
Fuller JC(2008)Assessment of programs for ligand binding affinity prediction J Comput Chem 8 1316-1331
[14]  
Burgoyne NJ(1997)The protein data bank Adv Drug Del Rev 23 3-25
[15]  
Jackson RM(2000)New method for fast and accurate binding-site identification and analysis Nucleic Acids Res 28 235-242
[16]  
Cheng AZ(1996)Identification of compounds with nanomolar binding affinity for checkpoint kinase-1 using knowledge-based virtual screening Proteins 26 363-376
[17]  
Coleman RG(2007)A Merck molecular force field: I-V Chem Biol Drug Des 69 146-148
[18]  
Smyth KT(2004)In vivo activation of the p53 pathway by small-molecule antagonists of MDM2 J Med Chem 47 1962-1968
[19]  
Cao Q(1996)Protein structure: discovering selective protein kinase inhibitors J Comput Chem 17 490-641
[20]  
Soulard P(2007)Crystallographic analysis of triclosan bound to enoyl reductase Chem Phys Lett 441 163-166
12345678910