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Simulating biology

Greg Blackman looks at some of the applications using HPC in the field of biomedicine

Images of the retina acquired with an OCT scanner and displayed inside Weill Cornell Medical College’s high-definition visualisation Cave. Image courtesy of Dr Luis Gracia, assistant imaging technology engineer at Weill Cornell


he complexity of biological systems means more researchers are turning to computing to better understand the

processes involved in biological pathways. Conducting experiments in silico will in no way replace hard actual biological research, whether that’s at the level of the cell or the organism, but it does guide researchers in the direction their work should take. At the University of London, the Cancer Research UK Protein-Protein Interactions Drug Discovery Research Group and the Biomolecular Structure Group within the School of Pharmacy are involved in a project modelling STAT transcription factors, believed to be instrumental in cancer signalling pathways.

The work revolves around molecular dynamic simulations of protein-protein and protein-DNA interactions, for which the National Grid Service (NGS) provides


computational time. Jarmila Husby, a researcher working on the project, explains: ‘We are hoping to see some conformational changes in the protein-DNA complex – how the transcription factor interacts with the DNA, what the nature of the conformational changes is, if there are any changes, and how it affects the function. Based on those simulations, the group will try and design potential small molecule inhibitors for these interactions to stop or limit the signalling process leading to cancer development.’ The transcription factors are important for cell development processes, but studies show that the proteins are overproduced in many types of cancer. Both proteins and DNA are large molecules and cannot be investigated as rigid bodies. Molecular dynamics allow these molecules to be understood better. Molecular dynamic simulations can be used to understand the physical basis of the


structure and function of biomolecules, such as proteins and nucleic acids. Within an MD simulation, molecules and atoms are allowed to interact according to known laws of physics, thereby giving an indication of the motion of the molecules over time. An important part of the simulation is the ‘force field’, which describes the interactions between the atoms within the molecules. A large protein or DNA molecule consists of many atoms and the computer simulation has to be able to describe the relationships and interactions between individual atoms. The simulation applies this force field to model the dynamics of the biomolecules and their conformational changes at the full atomistic scale of the complete biomolecular complex. ‘The biomolecular systems are very large,’

comments Husby, adding that the complex has 250,000 atoms and, in order to make the simulation as realistic as possible, the

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