By targeting a protein, and thus by extension the biological pathway in which that protein is involved, small molecules can be used to modulate a disease phenotype on a cellular, tissue or organism level. As the mode of action is often unknown, various experimental and in silico approaches have been used to connect the phenotype, the protein target or targets, and/or gene expression with the chemical structure and activity of a small compound(s) [1]. In contrast to the traditional ‘one drug – one target’ paradigm, the so-called ‘magical bullet theory’ as postulated by Ehrlich [2], compounds often modulate the (disease) phenotype by binding to multiple targets [3]. My research is focused on novel methodologies to predict the effect of a potential drug on the biological system. This would include deconvoluting its mode of action and assessing its side-profile (thus deriving an indication of potential side effects in the later clinniical stages).
References:
[1] Ravindranath, A. C. et al. Connecting gene expression data from connectivity map and in silico target predictions for small molecule mechanism-of-action analysis. Mol. BioSyst. 11, 86–96 (2015).
[2] Strebhardt, K. & Ullrich, A. Paul Ehrlich’ s magic bullet concept : 100 years of progress. Nat. Rev. cancer 8, 473–480 (2008).
[3] Brouwers, L., Iskar, M., Zeller, G., van Noort, V. & Bork, P. Network neighbors of drug targets contribute to drug side-effect similarity. PLoS One 6 (2011).