1. Molecular Modeling of the Human A1 Adenosine Receptor
Angela Bookwalter
Oral report #3
March 22, 1999
Advisor: Dr. Jack Wells
BME 273
Senior Design Project

2. Objective
The goal of this project is to design and test a three-dimensional molecular model of the seventh transmembrane-spanning region of the human A1 adenosine receptor.

3. Introduction Adenosine Receptor Purpose of designing model
G-protein coupled receptor
Reduces oxygen need of working cells
Prevents damage in short-term low-level oxygen situations
Purpose of designing model
Use as structure to design drugs and artificial ligands
Suggest information on functioning of receptor in biological situations

4. Introduction Design tools
Insight II version 97.0 molecular modeling software from Molecular Simulations, Inc.
Biochemical data from Wells Lab
Scientific literature

5. Design of 3-D Molecular Models
Complete Secondary Structure
Primary Structure
Simple Secondary Structure

6. Methodology Identification of transmembrane region
Hydrophobicity plots for 33 residues
Literature research
Lipid Membrane

7. Methodology Initial coordinates Addition of Biochemical Data
Selection from similar receptors to mesh with current known locations
Addition of Biochemical Data
Choosing of
Use of Additional Information Available

8. Methodology Energy and conformation calculations
Insight II software
Adjustments as dictated by mentors and additional biochemical data
Final analysis

9. Completed Work
Acquired basic knowledge of the Insight II software using tutorials
Preliminary structure analysis
Literature research
Development of modeling strategy
Preliminary design of secondary structure

10. Future Work Complete model of secondary structure of protein
Adjust model design as new data is acquired
Analysis of potential model designs - especially energy minimizations
Testing of final model design

11. Conclusion
The goal of this project will be achieved in the next week with a complete design which meets all desired specifications. Therefore, the project is progressing successfully and timely.