INFN IS BIOPHYS

Scientific and computational activity 2014

We summarize below the scientific and computational activities of the groups of the IS BIOPHYS that have accessed the Zefiro facility. 

Our IS has several research lines intersecting biophysics, computational physics and statistical mechanics. We investigate, for instance, the molecular mechanisms underlying genome regulation in eukaryotes, by combining their Statistical Physics description, computer simulations, and high-throughput data analysis. One of our research lines (developed mainly by the group in Napoli) regards chromosome spatial structure. Chromosomes have a complex 3D spatial organization serving vital functional purposes (e.g., related to cancer). The principles governing such a self-organization remain, though, elusive. We studied by Molecular Dynamics and Monte Carlo a polymer physics model where chromosome conformations are shaped by their interactions with other nuclear elements, including DNA-binding molecules. The model predicts definite conformational classes (and their 'scaling properties') and explains architectural transformations (via 'phase transitions') linked to, e.g., loci colocalization, chromosomal looping and territory formation. Our scenario explains for the first time all the currently available experimental results.

Another research line (developed mainly by the Tor Vergata group) concerns the study of structural properties of protein systems of medical and biological interest based on an integrated approach between experiments (AFM, X.ray, etc.) and classical molecular dynamics simulations. In particular, we mainly focused on:

- Thioflavin in interaction with the Abeta_40 amyloid peptide

- Betalactoglobulin alone and in interaction with Epicatechin molecules
 
- A proposal for an antitumor radioactive molecular vector based on an engineerized natural antimicrobial protein
We also studied the coordination properties of metal ions (e.g. Cu(2+)) in water based on a detailed comparison of experimental XAS data with molecular dynamics and ab initio computations. The QuantumESPRESSO and XSPECTRA suites have been used for the calculation of the electronic potential and the successive reconstruction of the X-ray signal, respectively.


The total amount of computer time employed by the group in the year 2014 was 450.000 core-hours (to be compared with the 300.000 assigned). As we are is serious need of CPU time, in 2015 we would like to ask for 500.000 core-hours on the Zefiro platform.


Paper published in 2014 by the groups of BIOPHYS accessing Zefiro

1)	M.G. Di Carlo, V. Minicozzi, V. Foderà , V. Militello, V. Vetri, S. Morante, M. Leone, “Thioflavin T controls Aβ(1-40) peptide conformation and templates its aggregation pathway.” BBA submitted

2)	G.L. Millhauser, V. Minicozzi, S. Morante, M. Pascucci, O. Proux, A. Spevacek, F. Stellato “Copper–Zinc cross-modulation in prion protein binding.” European Biophysical Journal (2014) 43: 631-642

3)	S. Morante, G.C. Rossi, “Metals in Alzheimer’s Disease: A Combined Experimental and Numerical Approach” in Advances in Alzheimer’s Research Volume 2: 100-147 DOI: 10.2174/97816080585251140201 eISBN: 978-1-60805-852-5, 2014 ISBN: 978-1-60805-853-2 ISSN: 2214-4358. 

4)	V. Minicozzi, R. Chiaraluce, V. Consalvi, C. Giordano, C. Narcisi, P. Punzi, G.C. Rossi and S. Morante, “Computational and experimental casus on beta sheet breakers targeting A1-40 fibrils.” J. Biol. Chem. (2014) 289, 11242-11252. 

5)	N. Christian, A.S. Skupin, S. Morante, K. Jansen, G.C. Rossi, O. Ebenhoeh “Mesoscopic behaviour from microscopic Markov dynamics and its application to calcium release channels” J. Theor. Biol. (2014) 343, 102–112. 

6)	D. Alesini, M. Alessandroni, M.P. Anania, S. Andreas, M. Angelone, A. Arcovito, F. Arnesano, M. Artioli et al. “IRIDE White Book, An Interdisciplinary Research Infrastructure based on Dual Electron linacs&lasers” (2014) Nucl. Instrum. Meth. (2014) A740, 138-146 DOI: 10.1016/j.nima.2013.11.040 

7)	A. Maiorana, T. Marino, V. Minicozzi, S. Morante, N. Russo. “A micro-environmental study of the Zn(II)-A1-16 structural properties” Biophysical Chemistry (2013) 182, 86-93

8)	G. La Penna, C. Hureau, P. Faller, “Learning chemistry with multiple first-principles simulations'” Mol. Sim. (2014)

9)	G. La Penna, C. Hureau, P. Faller, “A Cu-amyloid b complex activating Fenton chemistry in Alzheimer's disease: Learning with multiple first-principles simulations'', AIP Conference Proc. (2014), 1618(1), 112-114

10)	P. Faller, C. Hureau, G. La Penna, “Metal Ions and Intrinsically Disordered Proteins and Peptides: From Cu/Zn Amyloid- to General Principles'', Acc. Chem. Res. (2014) 47(8), 2252-2259,

11)	S. Furlan,, G. La Penna, D. Appelhans, M. Cangiotti, M.F. Ottavian,, A. Danani, “Combined EPR and Molecular Modeling Study of PPI Dendrimers Interacting with Copper Ions: Effect of Generation and Maltose Decoration” J. Phys. Chem. B, 118, 12098-12111 (2014),

12)	M. Zamparo, F. Chianale, C. Tebaldi, M. Cosentino Lagomarsino, M. Nicodemi, A. Gamba, “Dynamic membrane patterning, signal localization and polarity in living cells”, Soft Matter, in press (2015). 

13)	J.W. Armond, K. Saha, A. Rana, C. Oates, R. Jaenisch, M. Nicodemi, S. Mukherjee, “A stochastic model dissects cell states in biological transition”, Nature Scientific Reports 4, 3692 (2014).

14)	A. Pombo, M. Nicodemi, “Models of chromosome structure”, Current Opinion in Cell Biology 28, 90 (2014).

15)	A. Pombo, M. Nicodemi, “Physical mechanisms behind the large scale features of chromatin organization”, Transcription 5, e28447 (2014).

16)	F.P. Casale, G. Giurato, G. Nassa, J.W. Armond, C.J. Oates, D. Cora ́, A. Gamba, S. Mukherjee, A. Weisz, M. Nicodemi, “Single-Cell States in the Estrogen Response of Breast Cancer Cell Lines”, PLoS One 9, e88485 (2014).