Cardiovascular drug target identification via disordered protein analysis focus

Award Information
Agency: Department of Health and Human Services
Branch: N/A
Contract: 1R43HL083566-01A2
Agency Tracking Number: HL083566
Amount: $100,000.00
Phase: Phase I
Program: SBIR
Awards Year: 2007
Solicitation Year: 2007
Solicitation Topic Code: N/A
Solicitation Number: N/A
Small Business Information
6201 La Pas Trail, SUITE 160, INDIANAPOLIS, IN, 46268
DUNS: 183789163
HUBZone Owned: N
Woman Owned: Y
Socially and Economically Disadvantaged: Y
Principal Investigator
 VLADIMIR UVERSKY
 (317) 280-8737
 MAIN@MOLECULARKINETICS.COM
Business Contact
 YA J
Phone: (317) 280-8737
Email: yyvan@molecularkinetics.com
Research Institution
N/A
Abstract
DESCRIPTION (provided by applicant): A certain type of protein-protein interaction can be blocked using small molecules. This type of interaction involves a disorder-to-order transition of a molecular recognition element on one protein binding to a receptor site on another. Application of our proprietary bioinformatics software called PONDR(r) to a substantial set of cardiovascular disease (CVD)-associated proteins revealed that greater than 60% of these proteins are likely to contain disordered regions of substantial size and these regions contain a large number of molecular recognition elements. To exploit these preliminary findings, we will construct an annotated database of CVD proteins, "CardioVascular DisProt (CVD DisProt)," correlating disorder/order to proteins' functions. This new database will contain disorder/order predictions and existing structural knowledge correlated with collected functions of CVD-associated proteins and augmented with information of protein interaction networks. Next, our preliminary bioinformatics tools will be enhanced for the purpose of identifying druggable protein-protein interactions. The products developed in this project will form a new, powerful research tool, which will be used by pharmaceutical and biotechnology companies to improve prioritization of novel drug targets. CVD researchers could use relationships between function and order/disorder propensity to discover new proteins involved in signaling pathways of interest. Structural genomics centers would find CVD DisProt indispensable as a source of biologically relevant, ordered domains for structure determination. Finally, and most importantly, using the enhanced PONDR(r) tools, the CVD DisProt will be datamined to yield a ranked list of druggable protein-protein interactions. This will provide the starting point for a novel pathway for drug discovery.

* Information listed above is at the time of submission. *

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