Computational analysis of ligand relationships within target families

被引:53
作者
Bajorath, Juergen [1 ]
机构
[1] Rhein Freidrich Wilhelms Univ Bonn, LIMES Program Unit Chem Biol & Med Chem, BIT, Dept Life Sci Informat, D-53113 Bonn, Germany
关键词
D O I
10.1016/j.cbpa.2008.01.044
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Computational tools for the large-scale analysis and prediction of ligand-target interactions and the identification of small molecules having different selectivity profiles within target protein families complement research in chemical genetics and chemogenomics. For computational analysis and design, such tasks require a departure from the traditional focus on single targets, hit identification, and lead optimization. Recently, studies have been reported that profile compounds in silico against arrays of targets or systematically map ligand-target space. In order to identify small molecular probes that are suitable for chemical genetics applications, molecular diversity needs to be viewed in a way that partly differs from principles guiding conventional library design.
引用
收藏
页码:352 / 358
页数:7
相关论文
共 38 条
[1]   Virtual screen for ligands of orphan G protein-coupled receptors [J].
Bock, JR ;
Gough, DA .
JOURNAL OF CHEMICAL INFORMATION AND MODELING, 2005, 45 (05) :1402-1414
[2]   Chemogenomics: An emerging strategy for rapid target and drug discovery [J].
Bredel, M ;
Jacoby, E .
NATURE REVIEWS GENETICS, 2004, 5 (04) :262-275
[3]   Interaction profiles of protein kinase-inhibitor complexes and their application to virtual screening [J].
Chuaqui, C ;
Deng, Z ;
Singh, J .
JOURNAL OF MEDICINAL CHEMISTRY, 2005, 48 (01) :121-133
[4]   Robust ligand-based modeling of the biological targets of known drugs [J].
Cleves, Ann E. ;
Jain, Ajay N. .
JOURNAL OF MEDICINAL CHEMISTRY, 2006, 49 (10) :2921-2938
[5]   Structural interaction fingerprint (SIFt): A novel method for analyzing three-dimensional protein-ligand binding interactions [J].
Deng, Z ;
Chuaqui, C ;
Singh, J .
JOURNAL OF MEDICINAL CHEMISTRY, 2004, 47 (02) :337-344
[6]   A small molecule-kinase interaction map for clinical kinase inhibitors [J].
Fabian, MA ;
Biggs, WH ;
Treiber, DK ;
Atteridge, CE ;
Azimioara, MD ;
Benedetti, MG ;
Carter, TA ;
Ciceri, P ;
Edeen, PT ;
Floyd, M ;
Ford, JM ;
Galvin, M ;
Gerlach, JL ;
Grotzfeld, RM ;
Herrgard, S ;
Insko, DE ;
Insko, MA ;
Lai, AG ;
Lélias, JM ;
Mehta, SA ;
Milanov, ZV ;
Velasco, AM ;
Wodicka, LM ;
Patel, HK ;
Zarrinkar, PP ;
Lockhart, DJ .
NATURE BIOTECHNOLOGY, 2005, 23 (03) :329-336
[7]   Biospectra analysis: Model proteome characterizations for linking molecular structure and biological response [J].
Fliri, AF ;
Loging, WT ;
Thadeio, PF ;
Volkmann, RA .
JOURNAL OF MEDICINAL CHEMISTRY, 2005, 48 (22) :6918-6925
[8]   Biological spectra analysis: Linking biological activity profiles to molecular structure [J].
Fliri, AF ;
Loging, WT ;
Thadeio, PF ;
Volkmann, RA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (02) :261-266
[9]   Structure-activity relationship homology (SARAH): a conceptual framework for drug discovery in the genomic era [J].
Frye, SV .
CHEMISTRY & BIOLOGY, 1999, 6 (01) :R3-R7
[10]   Structure-based activity prediction for an enzyme of unknown function [J].
Hermann, Johannes C. ;
Marti-Arbona, Ricardo ;
Fedorov, Alexander A. ;
Fedorov, Elena ;
Almo, Steven C. ;
Shoichet, Brian K. ;
Raushel, Frank M. .
NATURE, 2007, 448 (7155) :775-U2