The overdue marriage of theory with experiment; a union facilitated by computational modelling.
Dr Mark Williamson and Dr Rubben Torella from Cambridge University's Unilever Centre will be sharing the stage.
With annual increases in computation power and technologies, application of theory via computation models is increasingly becoming a ubiquitous tool within research. Improvements in classical, all atom, modelling approaches of biological systems utilising molecular dynamics are providing closer agreement with empirical observables and providing further insight into underlying mechanisms. Here we present a spectrum of in silico approaches to investigate transcription factor-DNA recognition, validated by in vitro and in vivo analysis. We focused our study on CSL, one of the most important nuclear effectors within the Notch pathway. Initially, using the FOLDX tool, the relative binding energy (to CSL) of all possible permutations of DNA sequences, was calculated, ranked and then compared with previous experimental results. This indicated that CSL can bind a wider repertoire of DNA sequences in vitro and in vivo than previously known. Molecular dynamics simulations have been used to further study how CSL responds to the presence of different DNA sequences, indicating how DNA may act as an allosteric modulator in regulating CSL response to different DNA sequences in vivo. Finally, an in silico approach has been used to study how the DNA shape may affect the binding and the transcriptional regulation of CSL in vitro and in vivo, indicating how nucleotides flanking the DNA binding site may be as important as those directly interacting with the transcription factor.
If you would like to meet with the speakers, please contact their host Dr Patrick Varga-Weisz to make arrangements.