Protein Structure Computation
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Notes: PDF (600 KiB)
The sequencing of the human genome and subsequent expansion of understanding of the processes of the human body have brought great increases in the scope of therapeutic drug applications. In the past year, reports of possible treatments for diseases such as Alzheimer's, Huntington's, and multiple sclerosis have been seen; the common theme to these afflictions (and many others) is that they are caused or sustained by certain proteins. These molecules are of central importance to biochemistry. This presentation seeks to demonstrate how computer science can be and has been of benefit to research in this field.
Firstly, an introduction to the fundamental principles of protein structure and behaviour is given. Amino acids and peptide chains are described, and the four hierarchical abstractions of geometric arrangement explained 1. With this foundation prepared, the basic problems in computational biochemistry (folding, alignment and annotation, and docking) are outlined 2,3 and major existing techniques for their investigation reviewed 4.
Applications of solutions to the above problems are varied, but we focus on one of much interest worldwide at this time: that of rational drug development. This topic is described, with illustrations of real and current projects of both desktop and globally distributed scales 5,6. In particular, the use of the Fast Fourier Transform (FFT) for convolution-based correlation scoring is noted 7.
An implementation of a docking program employing the established FFT algorithm is presented, showing the uses and limitations of the method. The program offers Java classes for representing proteins and other molecules, along with an interface for docking algorithms. This permits several algorithms to be applied in turn to a pair of molecules, each progressively improving the quality of docking. Finally, the current status of the project is given, with the details of an optimisation stage to refine the initial results from an FFT execution, and proposed routes of investigation from that point onwards.