The overall aim of the proposed research is to study peptide hydrolysis within serine proteases by using novel density functional theory based mixed quantum-classical methodologies. Mixed quantum-classical methods are necessary to model chemical reactions in which there is bond breaking and formation. We propose to approach the problem in a stepwise fashion, breaking it down into relevant components.
Specific aim 1 plans to test various mixed quantum-classical potentials in their ability to adequately represent interactions within a peptide.
In specific aim 2 we propose to calculate a likely reaction pathway for ester hydrolysis. In doing so the structural changes that occur during the reaction will be investigated and analyzed. Then using information gained in both Specific Aims 1 and 2, the reaction will be modeled in a chymotrypsin enzyme mimic and in chymotrypsin itself. In this way much more will be learned regarding the role of the active site in peptide hydrolysis. These calculations are made possible, not only with the mixed quantum-classical methods but also through newly developed and efficient sampling algorithms to study complex biological reactions.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32GM019273-03
Application #
6150991
Study Section
Special Emphasis Panel (ZRG3-BBCA (03))
Program Officer
Marino, Pamela
Project Start
2000-02-01
Project End
Budget Start
2000-02-01
Budget End
2000-05-26
Support Year
3
Fiscal Year
2000
Total Cost
$13,361
Indirect Cost
Name
Boston University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
042250712
City
Boston
State
MA
Country
United States
Zip Code
02215