The Computational Biology theme of the department brings together several activities in the life sciences. We have a particular strength in computational structural biology, and host the Instruct computational centre. We host the core group for CCP4 in macromolecular crystallography, and host a similar group for CCP-EM (link opens in a new window) in biological electron cryo-microscopy. The PiMS (link opens in a new window) project is developing an information management system for protein production and crystallisation. We are active in biomolecular simulation, providing support for CCP-BioSim (link opens in a new window) and collaborating with experimental groups in STFC in a study of epidermal growth factor receptor. Finally, we lead a new theme in data-intensive biology, with a particular focus on next generation sequencing.
For more information about the Computational Biology team please contact Dr Martyn Winn. A list of current staff can be found on the staff pages.
MD simulations help us understand the dynamical properties of biological systems at the molecular, fully atomistic level. Projects we are currently involved in are described in the following.
We investigate membrane receptors, e.g. the epidermal growth factor receptor (EGFR) and ErbB family. ErbB receptors transduct signals from the cell surface through the membrane to the cytosolic tyrosine kinase where the signal is propagated in a cascade further down to launch certain cell processes. The ErbB receptor family is involved in growth, differentiation, and apoptosis of the cell. This signalling network is implicated in the development of most human cancers and hence is a prime target of anti-cancer molecular therapeutic agents (see Multi-million funded experiments could lead to revolution in cancer treatment (link opens in a new window)).
We use modelling and MD simulations to build and investigate models to explain FRET measurements taken by Marisa Martin-Fernandez' collaborating group.
The glutamine binding protein (GlnBP) is involved in the first stage of transporting glutamine (nutrient uptake) across the inner membrane of E. coli. GlnBP is the periplasmic - though not covalently bound - component of the corresponding ABC (ATP binding cassette) transport system. Upon ligand binding the 2-domain protein connected by a common hinge region undergoes an extreme conformational change. We are interested in the collective motions of GlnBP that are linked to its biological function. We also want to elucidate the closing mechanism of this protein. This project has been carried out in collaboration with Prof. Akio Kitao, Laboratory of Molecular Design (link opens in a new window), the University of Tokyo.
Whereas atomistic simulations can today reasonably be done for several hundred thousands to a few million atoms on the time scale of tens to hundreds of nano seconds, larger systems on a longer time scale are obviously still out of reach. To address this problem we apply CG simulations complementary to atomistic simulations. At the moment we are looking into the recent MARTINI force field (link opens in a new window) for lipids and proteins and assessing its value for membrane-receptor systems.
Molecular Replacement (MR) is one of the key methods available for determining protein structure from X-ray diffraction data. The method uses a trial structure to provide initial estimates of the phases.
Historically, ab initio models have been too inaccurate to give suitable phase estimates, and the method uses instead experimentally determined structures if these are available. The past few years have seen the progressive maturation of ab initio modelling, and we have been investigating the use of such models in MR to see if they are now reaching the required accuracy. While their use is clearly limited to certain sizes and classes of proteins, we have achieved some successes. (Read more ...)
We provide coarse-grained coordinate sets for various membrane bilayer arrangements. (more info)
We have extended the functionality of the ptraj utility (AMBER9/AmberTools 1.x) to include a few handy routines like computation of mean residence times and our own diffusion code. (more info)
We have a few Tcl jiffies to help analyse the geometries of proteins and lipids, for use with VMD. (more info)
We have prepared a CHARMM script to do MM-PBSA calculations and also provide results from a sample simulation to play with. (more info)