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Seminar by Dr. Valentina Tozzini

Scuola Normale Superiore, Pisa (Italy)

16 Sep 2014 10:00
16 Sep 2014 11:00
Lecture room 2009, Jülich GRS building (16.15)

Complex systems naturally display a hierarchical organization. This is particularly evident in biological macromolecules, where primary to quaternary structures are recognizable and are the basis of function of proteins and nucleic acids. However, organized structures on different scales are often present even in materials, either natural or artificial. As an example, graphene and its relatives display organization at the nano-scale, namely the size of fullerene, nanotubes and nano-sponges. The sizes of the considered systems generally span approximately ten orders of magnitude in the space domain (from Å to macroscopic scales) and twelve in the time domain (from ultra-fast photochemical reactions to diffusive motion) [1].
Theories of different levels of empiricism are used to address this complexity. At the “QM level” one considers both ions and electron explicitly, with virtually no adjustable parameters in the interactions. This allows treating up to hundreds or thousands of atoms (on high performance computational systems (HPC)) on the ps-ns time scale. To go beyond those scales, one must quit the explicit representation of electrons and treat the interatomic interactions by empirically “force fields”. Single processors allow simulation of hydrated proteins (up to 100000 atoms and the 100 ns long simulations). HPC allow reaching the virus size (~100 nm, tens of millions of atoms). The QM and MM levels are considered both for bio-systems and materials and are sometimes mixed in hybrid QM/MM approaches.
To go beyond, one enters the so-called coarse-grained (CG) domain [2], where groups of atoms are treated as a single interacting object (“bead”). The levels of coarse graining might depend on the kind of system: A typical level for bio-systems is a single bead per amino-acid or nucleotide (‘minimalist’ models [3]), but coarser levels up to a single bead per protein (‘meso-scale’) are also considered, which is also the scale level of fullerenes and nanotubes. This representation allows reaching macroscopic scales (e.g. diffusive motion within the cytoplasm [4]). Finally, the particle-like multi-level representations are often embedded in continuum representation of the solvent, which can be considered an extreme level of coarse graining. Furthermore, the 2D versions of continuum are used to model graphene or biological membranes.
After a summary of the multi-scale methods, the possible ways to combine them coherently will be highlighted. Applications will be then illustrated to a number of macromolecular biological systems (HIV-proteins [5,6], NA-protein complexes [7]) and to graphene related systems [8], and to processes with different time scales (photoreaction, chemical adhesion, vibrational dynamics, diffusion in different environments).


[1] V. Tozzini “Multi-Scale Modeling of Proteins”, Acc Chem Res, 43 220-230 (2010)
[2] V. Tozzini “Coarse Grained Models for Proteins” Curr Opinion Struct Biol 15 pp 144-150 (2005)
[3] V. Tozzini “Minimalist models for proteins: a comparative analysis”, Q Rev Biophys 43 , 333–371 (2010)
[4] F. Trovato, R. Nifosi, A. Di Fenza, V Tozzini “A minimalist model of proteins diffusion and interactions: the GFP within the cytoplasm”, Macromolecules, 46, 8311–8322, (2013)
[5] V. Tozzini, J. Trylska, C-E. Chang, J. A. McCammon “Flap opening dynamics in HIV-1 protease explored with a coarse-grained model” J Struct Biol 157 606-615 (2007)
[6] A. Di Fenza, W. Rocchia, V. Tozzini “Complexes of HIV-1 Integrase with HAT proteins: multiscale models, dynamics and hypotheses on allosteric sites of inhibition” Proteins 76, 946–958 (2009)
[7] K. Voltz, J. Trylska, V. Tozzini, V. Kurkal-Siebert, J. Langowski, J. Smith “Coarse-grained force field for the nucleosome from self-consistent multiscaling” J Comp Chem 29 1429-1439 (2008)
[8] V. Tozzini, V. Pellegrini “Reversible hydrogen storage by controlled buckling of graphene layers”, J Phys Chem C, 11525523-25528 (2011)