The objective of my research is to understand the function of complex biological systems and to unravel the basis of the molecular mechanisms by which such functions are achieved. Most biological systems – if not all – do not behave like solid rocks, but they are in fact dynamical objects that interconvert among several different conformational states. In many cases, a specific function is achieved by an interplay between structural and dynamical properties of the system. As a consequence, understanding the behaviour of biological systems requires the determination of a structural ensemble (A), defined by the structures of all the relevant states that these molecules can occupy, their populations, and the rates of interconversion among these states. This goal can be effectively achieved by using integrative approaches that combine experimental and computational techniques (B).
My research at Institut Pasteur is focused on the development of integrative modelling approaches for the determination of protein structural ensembles and their application to systems of outstanding biological importance. A recent field of application is the simultaneous determination of protein structure and dynamics by integrating cryo-electron microscopy data with other sources of theoretical and experimental information (C).
Relevant bibliography
[1] R.-A. A. Garibsingh et al. BioRxiv (2020) doi: 10.1101/2020.05.29.124305
[2] J. S. Fraser, K. Lindorff-Larsen, M. Bonomi. J. Chem. Inf. Model. 60 (2020) 2410
[3] The PLUMED consortium. Nat. Methods 16 (2019) 670
[4] L. Eshun-Wilson et al. Proc. Natl. Acad. Sci. USA 116 (2019) 10366
[5] M. Bonomi, R. Pellarin, M. Vendruscolo. Biophys. J. 114 (2018) 1604
[6] S. Vahidi et al. Proc. Natl. Acad. Sci. USA 115 (2018) E6447
[7] M. Bonomi, G. Heller, C. Camilloni, M. Vendruscolo. Curr. Opin. Struct. Biol. 42 (2017) 106
[8] M. Bonomi, C. Camilloni, A. Cavalli, M. Vendruscolo. Sci. Adv. 2 (2016) e1501177