The Elcock Group

Molecular Simulations in Biology

Movie Gallery

On this page you will find some movies that illustrate aspects of our research; these movies have been made with a variety of programs,including PyMol, VMD and some software written especially by Dr. Sean R. McGuffee. Feel free to view and download these movies if you can - unfortunately our server tends to run a bit slow at times (sometimes very slow: we’re not sure why yet) so if you have no success let AHE know and he’ll try to help out. Regarding the movies, the usual request applies: if you use them please don’t forget to cite the people who made them…

A Simulation of a Protein Solution

                                                                    This Brownian Dynamics simulation shows the diffusion and association of 1000 chymotrypsinogen molecules at a protein  concentration of 10g/l. All molecules in the simulation are identical but we have colored those in the middle red so that we can see how the molecules mix during the course of the simulation, which in this case, was conducted for 10 microseconds. The length of the simulation is sufficient that reasonably accurate radial distribution functions for the protein-protein interaction can be obtained: this in turn means that the second virial coefficient can be computed and compared with experiment.

This work was carried out by Dr. Sean R. McGuffee and published last year in the Journal of the American Chemical Society (pdf).

Substrates Channeling (or not) Between Enzyme Active Sites

                                                                    This BD simulation shows an oxaloacetate molecule (yellow) attempting, and failing, to ‘channel’ from the active site of Malate Dehydrogenase (red) to the active site of Citrate Synthase (blue). As is the case in the corresponding experimental studies of this system, the simulations also contain 10mM of malate (green/red molecules) - and these can be seen to be congregating in the active site of Citrate Synthase. The repulsive electrostatic interaction between these resident malate molecules and the diffusing oxaloacetate effectively prevent the latter reaching the active site…

This work was published in the Biophysical Journal in 2002 (pdf), where it basically sank without trace. Boohoo...

Crowding Effects on Protein Escape from GroEL

                                                                    The effects of macromolecular crowding on the kinetics and thermodynamics of protein folding and protein-protein association events are of considerable research interest currently. The simulation shown at the left was part of a study that we carried out investigating the effects of a typical crowding agent (Ficoll 70; green) on the escape probability of a substrate protein, rhodanese (red) from the chaperonin GroEL (blue). In this simulation the substrate protein is gradually ‘pulled’ out of the chaperonin and the free energy profile computed.

This work was published in the Proceedings of the National Academy of Sciences in 2003 (pdf).

Simulations of Cotranslational Protein Folding

                                                                    We have recently extended our BD methods to allow us to simulate protein synthesis and folding events. If you click on the left-hand side of the image you will see a BD simulation showing the synthesis of the small model protein Chymotrypsin Inhibitor 2 (CI2) performed under conditions in which the protein’s simulated stability matches that measured experimentally. If you click on the right-hand side of the image you will see a corresponding simulation in which the protein’s simulated stability has been artificially increased: in this case, the ribosome becomes ’constipated’ (sorry for the unsettling analogy) due to premature folding of the protein.

This work was published in the journal Public Library of Science : Computational Biology in 2006 (pdf).

Simulations of E. coli Cytoplasm

                                                                    Building on the work that he and I reported in J Am Chem Soc last year, Dr. Sean McGuffee has recently completed a series of BD simulations aimed at modeling GFP diffusion in the E. coli cytoplasm. The simulation shows 1000 individual macromolecules diffusing, colliding and transiently associating with each other over the course of a few microseconds simulation. You may recognize some of the macromolecular components in our model: e.g. the 50S and 30S ribosomal subunits are pretty conspicuous by their extreme reluctance to diffuse by any appreciable distance.

This work is currently being written up for publication...