Toward microscopic simulations of the cellular environment
speaker: Fabio Sterpone (IBPC)abstract: Proteins work in an extremely heterogeneous and crowded environment. Indeed 5 to 40% of the intracellular total volume is occupied by large biomolecules 1. This crowding condition a ects both the mobility and stability of a protein. Understanding the molecular details of proteins life in the cell is therefore considered a challenge for modern biophysics and molecular biology 2. Unfortunately, the experimental manipulation of the intracellular milieu is very dicult, as well as the in silico characterization of systems with such a large size and spread of length- and time-scales 3. We have recently developed a multi-scale multi-physics approach that enables us to investigate proteins in cell like environments via computer simulations 4. This approach combines molecular and fluid dynamics and allows to include naturally hydrodynamic interactions in water free coarse-grained model for biomolecules at the quasi-atomistic resolution. Back-mapping to all-atom resolution of sampled con gurations allows to estimate thermodynamics quantities via enhanced sampling 5. In this talk we will describe the methodologies, their integration, and showcase the ensemble of applications currently on the way. This includes the study of amyloid peptide aggregation (the hallmark of neurodegenerative diseases like Alzheimer), the mobility and stability of proteins in crowded environment. 1 R. J. Ellis, A. P. Minton, Nature 2003, 425,27-28. 2 a) I.Guzman,M.Gruebele, J Phys Chem 2014,118,8459. b) M.Sarkar,A.E. Smith, G.J. PNAS 2013, 110, 19342-19347. 3 a) S.R. McGu ee, A. H. Elcock, PLoS Comput Biol 2010, 6,e1000694. b) I. Ku et al, eLife 2016, 5, e19274 4 a) F.Sterpone, P. Derreumaux, S. Melchionna, J Chem Theory Comput 2015, 11, 1843-1853. b) F. Sterpone et al, Chem Soc Rev 2014, 43, 4871-4893. c) M. Chiricotto et al, J. Chem. Phys. 2016, 145, 035102. d) M. Chiricotto et al, Phil. Trans. 2016 374 20160225. e) Sterpone et al, BBRC 2017, in press. 5 Katava, et al, PNAS (2017), 114, 93619366, G. Stirnemann and F. Sterpone, JPCL (2017), , 8, 58845890
timetable:
Mon 1 Oct, 15:15 - 16:30, Aula Dini
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