To:tidor@mit.edu
cc:
Subject:UROP proposal
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Dear Professor Tidor,
	This is my UROP proposal:



Atomic Interactions Responsible for the Binding of Enzyme Inhibitors

	This project is a study of the thermodynamics of biomolecules to gain an
understanding of the mechanisms of inhibiting enzymes. The goal is to develop a
theory of how competitive inhibitors are optimally bound to the active site of
enzymes. To perform this research, the project will use approaches in continuum
electrostatic modeling recently developed by Professor Tidor's lab. The idea
behind this technique is that there is a charge for an inhibitor that optimizes
the inhibitor's binding with a charged active site. When the inhibitor has this
optimal charge it will have the energetically most favorable interaction with
the enzyme.  
	My project will be a detailed analysis using known X-ray crystal
structures of protien complexes. With these I will determine how the secondary
structure of the active site of the enzyme affects inhibitor binding. In order
to do this, I will first need to use the protein data base libraries on the
internet to find a group of enzymes with interesting docking sites - the
location where an inhibitor binds to the active site. Then using the known X-ray
crystallographic coordinates of these enzymes, I will perform detailed
thermodynamic based computations of how charged molecules interact with
variously charged secondary structures -alpha helixes, beta sheets, and loops.
	I'm interested in studying biological molecules from a structural and
biophysical perspective. Furthermore, I plan to pursue knowledge in this field
during my undergraduate studies and I'm excited to begin with this research.


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I'm really grateful you're looking this over, and if you would like me to stop
by your office please e-me. Monday I can stop by anytime before 10 or after 12,
and Tuesday I can meet anytime between 12 and 2:30. Also, these are some
questions that are puzzling me: 

I'm curious if there is a specific group of enzymes that I'm going to search;
and what makes an enzyme's active site interesting?
Do I need to give more describe the methods of the detailed analysis of the
X-ray crystal structures?

Thank you very much,
Bryant

