Gwyn SkonePublications


Doctoral Thesis:

Stratagems for Effective Function Evaluation in Computational Chemistry
Oxford, 2010


Doing a Good Turn: The Use of Quaternions for Rotation in Molecular Docking
J. Chem. Inf. Model. 2013
Knowing When To Give Up: Early-Rejection Stratagems in Ligand Docking
J. Comput. Aided Mol. Des. 2009
Protein Structure Computation
Proc. FBIT 2007


Basic Strategies for Molecular Docking with Scoring Functions
German Conf. Bioinf. 2008


Knowing When To Give Up: Sensible Evaluation in Virtual Screening for Drug Discovery
OUCL Cakes Talk. 2008
Protein Structure Computation
Proc. OUCL PRG Student Conf. 2006

Protein Structure Computation

Gwyn Skone
In Proceedings of The Oxford University Computing Laboratory Programming Research Group Student Conference 2006.


Slides: PowerPoint (569 KiB)

Notes: PDF (600 KiB)


Conference abstract book


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.


  1. Branden, C., and Tooze, J.: Introduction to Protein Structure. 2 ed. (1999). Garland. 0-815-32305-0.
  2. Richards, F.M.: Areas, Volumes, Packing, and Protein Structure. Ann. Rev. Biophys. Bioeng., 6 (1977), 151-176. Annual Reviews.
  3. Sinha, N., and Smith-Gill, S.J.: Protein Structure to Function via Dynamics. Protein Pept. Lett., 9 (2002) 367-377. Bentham.
  4. Connolly, M.L.: Molecular Surfaces: A Review. (1996)
  5. Richards, W.G.: Virtual screening using grid computing - the screensaver project. Nature Reviews (Drug Discovery), 1 (2002) 551-555. Nature Publishing.
  6. Venkatachalam, C.M., Jiang, X., Oldfield, T., and Waldman, M.: LigandFit: a novel method for the shape-directed rapid docking of ligands to protein active sites. J. Mol. Graph. Model. 21 (2003) 289-307. Elsevier Science.
  7. Katchalski-Katzir, E., Shariv, I., Eisenstein, M., Friesem, A.A., Aflalo, C., and Vakser, I.A.: Molecular Surface Recognition: Determination of geometric fit between proteins and their ligands by correlation techniques. Proc. Natl. Acad. Sci. USA. 89 (1992) 2195-2199. National Academy of Sciences.