Understanding dynamical processes Understanding dynamical processes

A considerable amount of information is known about a proteins static geometric structure. Proteins however are not static entities and are in fact molecular machines that are involved in every biological process.

Protein dynamics is relatively unstudied subject yet it is only through the understanding of a proteins dynamical process that a proteins function can be truly understood. Of particular biophysical interest is the response from a protein during the process of binding with a ligand i.e. a drug molecule. These responses take the form of an external force that will be exerted on the protein as the ligand attempts to enter the active site. Therefore it is important to understand the response a protein would have to externally applied forces. This can be greatly facilitated through the use of computer simulation and haptic feedback where a user can see and feel the response from the protein as they apply forces in real time. The remainder of this page contains a background into the research undertaken in the field of molecular graphics and simulation.

Background

The structures of a large number of protein structures have been solved, meaning their geometric information has been determined to atomic resolution. This can be combined with the knowledge of inter-molecular and inter-atomic forces known as force fields in a computer simulation to aid in the understanding of the molecules bio-mechanical properties. A user can then observe the behaviour of the protein by placing a ligand at varying distances from the active site. This process is generally referred to as "docking" and attempts have previously been made to combine this process with molecular graphics and incorporation of haptic feedback in a small number of software packages with varying degrees of success.

Our Research

Previous software attempting this process uses a process of coupling the haptic device to the molecular dynamics simulator in order to gain the information required for the correct feedback response. This requires a large amount of computing power as well as a scaling system required to couple human reaction time scales that span minutes and hours with protein time scales that span nano-seconds or less. Our approach decouples the expensive molecular dynamics simulation from the process eventually leading to a viable tool for biological research and study.

Interactive Solvent Accessible Surface

Our initial work in this area led to the development of new haptic rendering algorithms for interacting with the space filling representation of molecules utilising a probe sphere. If this probe has the radius of a water molecule it can be considered to be interacting with the protein's solvent accessible surface.

Software can be downloaded free from www.haptimol.co.uk.

Elastic Network Models

Elastic network models (ENM) of biomolecules have proved to be relatively good at predicting global conformational changes, particularly in large systems. HaptiMOL ENM is software that facilitates rapid and intuitive exploration of conformational change in elastic network models of large biomolecules in response to externally applied forces.

Users are able to apply forces to individual atoms using a haptic (force) feedback device. The user feels the response to the applied force through the haptic device, whilst seeing the deformation on the screen.

Selected Publications

  1. Stocks, M.B., Laycock, S.D. and Hayward, S., Applying forces to elastic network models of large biomolecules using a haptic feedback device, Journal of Computer-Aided Molecular Design, 2011.
  2. Laycock, S.D., Stocks, M.B. and Hayward, S., Navigation and exploration of large data-sets using a haptic feedback device, ACM Siggraph: Posters, 2010.
  3. Stocks, M.B., Hayward, S. and Laycock, S.D., Interacting with the biomolecular solvent accessible surface via a haptic feedback device, BMC Structural Biology, 9:69, 2009.
  4. Stocks, M.B. and Laycock, S.D., A Haptic Rendering Algorithm for Molecular Interaction, Eurographics Workshop on Visual Computing for Biomedicine, Delft, The Netherlands, pp. 37-44, October, 2008.
  5. Laycock, S.D. and Day, A.M., A Survey of Haptic Rendering Techniques, Computer Graphics Forum, vol. 26, no. 1, pp. 50-65, 2007.
  6. Laycock, S. D. and Day, A. M., Recent Developments and Applications of Haptic Devices. Computer Graphics Forum, Volume 22, Issue 2, Page(s) 117-132, 2003.

Research Team

Mr. Georgios Iakovou, Dr. Matthew B. Stocks, Dr. Stephen Laycock, Dr. Stephen Hayward