Computational techniques in fragment based drug discovery

被引:16
作者
Villar, Hugo O. [1 ]
Hansen, Mark R. [1 ]
机构
[1] Altoris Inc, La Jolla, CA USA
关键词
D O I
10.2174/156802607782194725
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Fragment based drug discovery is gaining acceptance as a complement to other more established techniques to identify leads and optimize drug candidates. In this review we illustrate areas where fragment based drug discovery has had an impact and point to some examples that show how fragment based analysis is being applied to new arenas. The traditional uses of computational methods in fragment based for lead discovery and optimization and for risk assessment are briefly summarized. The application of fragment analysis for the definition of bioisosteric replacements are discussed together with techniques to characterize the diversity of chemical libraries based on fragment distribution.
引用
收藏
页码:1509 / 1513
页数:5
相关论文
共 60 条
[41]   Locating and characterizing binding sites on proteins [J].
Mattos, C ;
Ringe, D .
NATURE BIOTECHNOLOGY, 1996, 14 (05) :595-599
[42]   Proteins in organic solvents [J].
Mattos, C ;
Ringe, D .
CURRENT OPINION IN STRUCTURAL BIOLOGY, 2001, 11 (06) :761-764
[43]   Design and characterization of a functional library for NMR screening against novel protein targets [J].
Mercier, Kelly A. ;
Germer, Katherine ;
Powers, Robert .
COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING, 2006, 9 (07) :515-534
[44]   A fragment-based approach to understanding inhibition of 1-deoxy-D-xylulose-5-phosphate reductoisomerase [J].
Merklé, L ;
de Andrés-Gómez, A ;
Dick, B ;
Cox, RJ ;
Godfrey, CRA .
CHEMBIOCHEM, 2005, 6 (10) :1866-1874
[45]   Automated protein-ligand crystallography for structure-based drug design [J].
Mooij, Wijnand T. M. ;
Hartshorn, Michael J. ;
Tickle, Ian J. ;
Sharff, Andrew J. ;
Verdonk, Marcel L. ;
Jhoti, Harren .
CHEMMEDCHEM, 2006, 1 (08) :827-838
[46]   BREED: Generating novel inhibitors through hybridization of known ligands. Application to CDK2, P38, and HIV protease [J].
Pierce, AC ;
Rao, G ;
Bemis, GW .
JOURNAL OF MEDICINAL CHEMISTRY, 2004, 47 (11) :2768-2775
[47]   What makes a binding site a binding site? [J].
Ringe, D .
CURRENT OPINION IN STRUCTURAL BIOLOGY, 1995, 5 (06) :825-829
[48]   Building a tree of knowledge: Analysis of bitter molecules [J].
Rodgers, S ;
Busch, J ;
Peters, H ;
Christ-Hazelhof, E .
CHEMICAL SENSES, 2005, 30 (07) :547-557
[49]   Computational prediction of the chromosome-damaging potential of chemicals [J].
Rothfuss, Andreas ;
Steger-Hartmann, Thomas ;
Heinrich, Nikolaus ;
Wichard, Joerg .
CHEMICAL RESEARCH IN TOXICOLOGY, 2006, 19 (10) :1313-1319
[50]   In silico fragment-based discovery of DPP-IV S1 pocket binders [J].
Rummey, C ;
Nordhoff, S ;
Thiemann, M ;
Metz, G .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2006, 16 (05) :1405-1409