Research and Deployment of a quantum mechanical NMR tool for fragment based drug

Award Information
Agency:
Department of Health and Human Services
Branch
n/a
Amount:
$1,070,708.00
Award Year:
2012
Program:
SBIR
Phase:
Phase II
Contract:
4R44GM099411-02
Award Id:
n/a
Agency Tracking Number:
R44GM099411
Solicitation Year:
2012
Solicitation Topic Code:
NIGMS
Solicitation Number:
PA10-050
Small Business Information
200 INNOVATION PARK, STE 261, STATE COLLEGE, PA, -
Hubzone Owned:
N
Minority Owned:
N
Woman Owned:
N
Duns:
172210572
Principal Investigator:
LANCE WESTERHOFF
(814) 235-6908
lance@quantumbioinc.com
Business Contact:
LANCE WESTERHOFF
(814) 235-6908
lance@quantumbioinc.com
Research Institution:
Stub




Abstract
DESCRIPTION (provided by applicant): Improving human health by enabling the development of drugs faster and cheaper is an important part of the NIH mission. This is partially achieved by introducing and constantly improving enabling technologies. One suchtechnology is structure based drug design. Determining the structure of a small molecule (drug candidate or lead compound) to a biological receptor (protein implicated in disease) is a necessary step in this methodology. The dominant experimental approachused to achieve this goal is X- ray crystallography, while nuclear magnetic resonance (NMR) plays a lesser role in spite of large investments both in academia and industry. NMR is hampered by the size of protein that can be studied and the need to go through a lengthy structure determination process. However, with the advent of fragment based drug design, NMR is playing a much larger role and it could play an even greater role if it was possible to reduce the time effort necessary to solve the structure ofa protein-ligand complex. Moreover, in cases where it is not possible to obtain a crystal NMR can play a significant role. Through the use of solid-state NMR studies membrane proteins or proteins with solubility problems can be studied or in cases where only homology models of a protein are available NMR could play a role through the validation of active site structure hypotheses generated in homology modeling studies. The aim of the proposed research is to extend and commercialize QuantumBio's successful linear-scaling semiempirical quantum mechanical NMR approach (NMRScore) to chemical shift perturbation (CSP) analysis through the addition of target-observed CSP and ab initio NMR methods. In Phase I of this proposal the limits of applicability will be explored. In the Phase II proposal extension of the methodology via reparameterization of 1H, 13C 17O and 15N NMR will be carried out and a new classical NMR predictor will be developed. Furthermore, the streamlining of the workflow will be researched and implemented. Finally, this proposal is aiming to fully productize and commercialize this breakthrough technology. It is anticipated that by making this application commercially available the use of NMR in structure-based design efforts will be enhanced and theNMR tool and service market size can be further expanded. Significantly, the tool-box of structure based drug design will gain an important new method which will enable drug development for targets inaccessible to today's mainstream drug discovery paradigm. Thus, in the near future important underserved diseases can be targeted more efficiently.

* information listed above is at the time of submission.

Agency Micro-sites


SBA logo

Department of Agriculture logo

Department of Commerce logo

Department of Defense logo

Department of Education logo

Department of Energy logo

Department of Health and Human Services logo

Department of Homeland Security logo

Department of Transportation logo

Enviromental Protection Agency logo

National Aeronautics and Space Administration logo

National Science Foundation logo
US Flag An Official Website of the United States Government