Version 2.1.1.0

Abstract

Grant Number:	1R43GM067312-01
PI Name:	MURPHY, ROBERT B.
PI Email:	murphy@schrodinger.com
PI Title:
Project Title:	Modeling Metal-Containing Biological Systems

Abstract: DESCRIPTION (provided by applicant): 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.

Thesaurus Terms:
biophysics, chemical model, computer program /software, computer simulation, computer system design /evaluation, metal complex, molecular dynamics, quantum chemistry
DNA binding protein, ligand, metal metabolism, metalloendopeptidase, receptor binding
bioengineering /biomedical engineering

Institution:	SCHRODINGER, INC.
	1500 SW 1ST AVE, STE 1180
	PORTLAND, OR 97201
Fiscal Year:	2003
Department:
Project Start:	01-APR-2003
Project End:	31-MAR-2004
ICD:	NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
IRG:	ZRG1

---