Schrodinger's QSite is a mixed quantum mechanics/molecular mechanics (QM/MM) program specifically targeted to biological applications. QSite is based on a pairing of Jaguar [with its fast pseudospectral implementation of density functional theory (DFT) and other ab initio methods] and Impact (a protein modeling package which employs the OPLS-AA force field). As part of Schrodinger's First Discovery suite, which also includes Glide, a high-throughput docking program, and Liaison, a ligand-receptor binding energy program, QSite has already been demonstrated to be a powerful new tool for studying the reactive chemistry of metalloenzymes. Under this Phase I proposal, QSite's capabilities will be extended by adding a synchronous transit transition state search algorithm, completing the set of parameterized QM/MM interface cuts for amino acids, and parameterizing QM/MM cuts for nucleic acids. These developments will greatly enhance QSite's robustness in characterizing the reactive chemistry of bioinorganic systems, as well as extend the range of potential applications. A proof of concept study on ligand docking to a Zn matrix metalloproteinase will also be performed, demonstrating another potential role for the program in the lead optimization process.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
Project #
1R43GM067312-01
Application #
6583542
Study Section
Special Emphasis Panel (ZRG1-SSS-L (10))
Program Officer
Wehrle, Janna P
Project Start
2003-04-01
Project End
2004-03-31
Budget Start
2003-04-01
Budget End
2004-03-31
Support Year
1
Fiscal Year
2003
Total Cost
$99,987
Indirect Cost
Name
Schrodinger, Inc.
Department
Type
DUNS #
836320531
City
Portland
State
OR
Country
United States
Zip Code
97204