Publication Date:
2009-04-11
Description:
Structure-based drug design traditionally uses static protein models as inspirations for focusing on "active" site targets. Allosteric regulation of biological macromolecules, however, is affected by both conformational and dynamic properties of the protein or protein complex and can potentially lead to more avenues for therapeutic development. We discuss the advantages of searching for molecules that conformationally trap a macromolecule in its inactive state. Although multiple methodologies exist to probe protein dynamics and ligand binding, our current discussion highlights the use of nuclear magnetic resonance spectroscopy in the drug discovery and design process.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2981433/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2981433/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Gregory M -- Craik, Charles S -- 1R01A1067423/PHS HHS/ -- P30-AI027763/AI/NIAID NIH HHS/ -- P50 GM082250/GM/NIGMS NIH HHS/ -- P50 GM082250-02/GM/NIGMS NIH HHS/ -- R01 AI067423/AI/NIAID NIH HHS/ -- R01 AI067423-01A1/AI/NIAID NIH HHS/ -- R01 AI067423-02/AI/NIAID NIH HHS/ -- R01 AI067423-03/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2009 Apr 10;324(5924):213-5. doi: 10.1126/science.1169378.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmaceutical Chemistry, University of California, San Francisco (UCSF), 600 16th Street, Box 2280, San Francisco, CA 94158-2280, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19359579" target="_blank"〉PubMed〈/a〉
Keywords:
Allosteric Regulation
;
Allosteric Site
;
Apoproteins/chemistry/metabolism
;
Benzamides
;
CREB-Binding Protein/chemistry/metabolism
;
Catalytic Domain
;
Cyclic AMP Response Element-Binding Protein/chemistry/metabolism
;
*Drug Design
;
*Drug Discovery
;
Enzyme Inhibitors/chemistry/pharmacology
;
Imatinib Mesylate
;
Ligands
;
Nuclear Magnetic Resonance, Biomolecular
;
Piperazines/metabolism/pharmacology
;
Protein Binding
;
*Protein Conformation
;
Protein Multimerization
;
Protein-Tyrosine Kinases/antagonists & inhibitors
;
Proteins/antagonists & inhibitors/*chemistry/metabolism
;
Proto-Oncogene Proteins c-mdm2/chemistry/metabolism
;
Pyrimidines/metabolism/pharmacology
;
Signal Transduction
;
Small Molecule Libraries
;
Thermodynamics
;
Tumor Suppressor Protein p53/chemistry/metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
