Introduction
I'm Alex Macdonald, a 3rd year PhD research student studying in the Structures Group at Cambridge University under the supervision of Dr. Simon Guest. I previously studied Civil Engineering at Strathclyde University where I obtained my BEng degree in Civil Engineering before completing an MSc in Structural Engineering at Glasgow University. This page gives some information about what I am currently investigating, my research interests and my teaching commitments.
Current Research
My PhD research involves creating computational methods for calculating rigid regions within proteins and mapping the conformational space of the protein. Previous attempts to use rigidity theory to calculate a protein's conformation space have been moderately successful, but we believe our method has a distinct advantage in that the first order infinitesimal motions are produced by the computation.
We are currently testing our tools and methodology on the ATP/ADP (AAC) translocator in the inner mitochondrial membrane. From the atomic coordinates in the PDB file, we define the constraint network, comprising of covalent bonds, angular and planar constraints and constraints provided by hydrogen bonds, salt bridges and disulphide bonds. We then undertake a rigid region decomposition. This reduces the conformation space of the protein, making the calculation of the configuration space more tractable. The methodology is explained in the figure below. |
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atomic coordinates |
rigid region decomposition |
conformation mapping |
rigid region decomposition and movement |
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Using the compatibility matrices from the above computations, we can also create a protein stiffness matrix and identify the normal mode shapes of the protein. Some normal mode shapes of secondary structure elements are detailed in the figure below.
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beta sheet twist mode |
alpha helix bend mode |
alpha helix torsional mode |
secondary structure normal mode shapes |
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Publications
- 2007
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Macdonald, A.D. , "Protein Kinematics ", First Year PhD Progress Report, University of Cambridge. [PDF]
Presentations
- 2008
- Unified Rigidity and Kinematic Analysis of Proteins - Presented at Rigidity, Flexibility, and Motion: Theory, Computation and Applications to Biomolecules, Banff, Canada, July 2008. [PPT]
Posters
- 2009
- Protein Mechanics - Poster for Set for Britain poster competition, presented March 9th 2009 at the UK Parliament. [PDF]
- 2008
- Protein Kinematics - Poster for Vitae EE Hub poster competition, presented December 4th 2008. [PDF]
- 2008
- Simple Kinematic Analysis of Proteins - Poster for Imperial College London Bioengineering '08 Symposium. 18th - 19th September 2008 [PDF]
Teaching
For the 2008/2009 academic year I demonstrate and supervise the following courses:
IB Structures (supervision of Downing students)
3D4 Elasticity Analysis and Stability, Lent term
1A Structures , Truss Analysis (demonstrator)
Contact Details
E-mail: adm59@cam.ac.uk
Telephone: +44 (0)1223 (7)66682
Office: S2 Office, Department of Engineering, Trumpington Street, Cambridge, CB2 1PZ
College: Corpus Christi
Related Websites
Flexweb - Protein Rigidity and Conformation Analysis
Linkage - Rigidity and Pebble games
CCPB - Collaborative Computational Project for Biomolecular Simulation
TEST - Test page for CARET