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LBT/IBPC

13 rue Pierre et Marie Curie, 75005 Paris, FR

office 332

tel :: +33-1-58415169

fax :: +33-1-58415020



"I've…seen things you people wouldn't believe"

EDUCATION//CAREER ::

2018-present / Research Director

2011-2016 Award ERC starting Grant Thermos

2012 HDR (25 may)

2010--present / Research at CNRS

2009--2010 / Fellow "P-G de Gennes Fundation", ENS, Paris, FR

2006--2008 / Research at High Performance Computing CASPUR, Rome, IT

2004--2006 / Post-doc UT at Austin, TX, US

2000--2004 / PhD, UPMC and CEA, Saclay, FR

1999 / Laurea, Univ La Sapienza, Physics, Rome, IT

RESEARCH

We are interested in the multi-scale modeling of biophysical processes. We apply and develop methods for studying protein stability and function in different conditions and environments. We move from atomistic to coarse-graining/nanoscale descriptions.

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REPRESENTATIVE PUBLICATIONS

1. M. Katava, G. Stirnemann, M. Zanatta, S. Capaccioli, M. Pacchetti, K. Ngai, F. Sterpone, A. Paciaroni, «Critical structural fluctuations of proteins at the thermal unfolding: challenging the Lindemann criterion», (2017), PNAS, 114, 9361–9366.

2. G. Stirnemann, F. Sterpone, "Mechanics of Protein Adaptation to High Temperatures", J. Phys. Chem. Lett.,(2017), 8, 5884–5890.

3. F. Sterpone, P. Derreumaux, S. Melchionna «Protein simulations in fluids: coupling the OPEP coarse-grained force field with hydrodynamics», J. Chem. Theory Comput. (2015) 11, 1843-1853.

4. M. Chiricotto, S. Melchionna, P. Derreumaux, F. Sterpone, «Hydrodynamic effects on β-amyloid (16-22) peptide aggregation», J. Chem. Phys. (2016), 145, 035102.

5. M. Kalimeri, O. Rahaman, S. Melchionna, F. Sterpone, « How Conformational Flexibility Stabilizes the Hyperthermophilic Elongation Factor G-Domain », J. Phys. Chem . B (2013), 117, 13775-13785.

HIGHLIGHTS

>> The Amlet curse of a protein. The crossover stability under crowding.

The Hamlet curse of a protein: to be or not stabilized by the crowd. Question is: if excluded volume stabilizes the native state in the interior of a cell this means entropy rules. But, if not, this means the enthalpy contribution from local protein-protein interactions engage. Unfortunately, to make the story just a bit more complicate, temperature may alter the balance of the force. In short, do we need a thermodynamic version of Shakespeare? Or maybe just detect the crossover!

>> 11/2020. Tribute to PJ Rossky. To a great scientist, mentor and friend. Enjoy a nice collection of science here.

>> Be hot, be cool. Life on Earth exhibits an amazing adaptive capacity.

Organisms can thrive in extremes conditions, from glacial water (0°C) to hot springs (100°C). An amazing view of this adaptation is given by the color gradient in Yellowstone’s hot springs. A puzzling question is how organisms can fight the degrading action of temperature, and more, how they optimize the chemical processes of their metabolism as function of the living temperature. To answer this, we need to go down to proteins, soft-matter entities, that make life in action. Some interesting aspects are discussed in two twin-papers just out. Enjoy them! https://lnkd.in/d7EMs4r and https://lnkd.in/dEnhVjZ.

>> 9/2020. Welcome E. Laborie. Emeline just joined the lab. For her PhD research, she will use multi-scale modelling to investigate viral adhesion and localalization, and blood coagulation.

>> Excluded Volume Effect on Protein Stability. The experience of crowding.

To feel the concept, try to stretch and move in a crowded space, like in an underground train at rush hours. I can suggest RER B in Paris or Line A at Furio Camillo in Rome at 18h. Difficult, right? Well this is what happens in vivo inside cells where proteins experience a permanent fluctuating crowded environment made up by proteins, RNAs, DNAs, lipids, osmolytes, ions. The effect can be formalized in physical concepts. Moving under crowding means for instance that the diffusion occurs in a space of reduced dimensionality. Stretching becomes difficult because the space available for the associated movement is reduced, we lose entropy! Again, a little game helps: try to extend a pearl-necklace in a small jewel box, if the box is too small no way to succeed. To help visualizing the reality for proteins get a look at the video. We overlapped the unfolding states of SOD1 to the sampled trajectory of SOD1 in a cell-like crowded solution. To enjoy the real science, get a look at the paper here (https://lnkd.in/dgbshgY).


>>PRACE award CELLPHY "Diffusion and Stability of Proteins in Cell-like environments." We will investigate into the detail of a protein mobility and stability in a crowded environment via multi-scale simulations based on Lattice Boltzmann Molecular Dynamics. All the calculations will be performed at CINECA HPC using the novel machine MARCONI.

>>How solvent mediated interactions drive amyloid aggregation... get a look to out work just our in JCP "Hydrodynamic effect on Ab(16-22) peptide aggregation" [see here]. Also, if you look for a broad overview of the application of the LBMD technique "Multiscale simulation of molecular processes in cellular environments" in Phil. Trans. [see here]

>> Challenging massive aggregation of amyloid short peptides: this was the goal of the computational BigChallenged2015. IDRIS HPC center awarded us a special allocation of time on Turing (Blue/Gene Q) to test our LBMD technique. [see here]

>> Functioning at high T: by mimicking the enzymatic turnover of two homologous GTPase domains we explore how functional modes respond to substrate binding/hydrolysis at different temperatures. "Stability and Function at High Temperature. What Makes a Thermophilic GTPase Different from Its Mesophilic Homologue" [see here]

>> Thermal stability: A challenge for in silico study. We have proposed a approximate scheme for performing enhanced sampling and recovering the stability curve of small proteins via Hamiltonian Replica Exchange. "Recovering Protein Thermal Stability Using All-Atom Hamiltonian Replica-Exchange Simulations in Explicit Solvent" [see here]

>> Proteins in fluid. We provide an extended description of a novel simulation framework for including hydrodynamic interactions in protein simulations based on water-free coarse-grained models. "Protein Simulations in Fluids: Coupling the OPEP Coarse-Grained Force Field with Hydrodynamics" [see here]

>> Stay wet stay stable. A work recently accepted and to be published in Branka Ladanyi Festschrift JPCB. "Role of Internal Water on Protein Thermal Stability: The Case of Homologous G Domains" [see here]

>> How thermophilic multi-domain proteins secure their fold at high T ? "Interface Matters: The Stiffness Route to Stability of a Thermophilic Tetrameric Malate Dehydrogenase" [see here]

>> A new work where the the coarse-grained model OPEP is used to investigate thermal stability: "Are coarse-grained models apt to detect protein thermal stability? The case of OPEP force field" [see here].

>> A review on the coarse-grained model OPEP is just out in Chem.Soc.Rev. "The OPEP protein model: from single molecules, amyloid formation, crowding and hydrodynamics to DNA/RNA systems" [see here].

"…The OPEPv4 model was used to explore the thermal stability of two homologues, the G-domains of EF-Tu and 1a proteins. These 200-aa domains were simulated by REMD using 24 replicas spanning 260–580 K, each for 300 ns…"

>> The crew of ResearchMedia publishes an highlight of the project THERMOS in the International Innovation magazine: "Towards new thermostable proteins"

...In the THERMOS project underway at the Laboratoire de Biochimie Théorique in France, original and diverse computational approaches aim to determine new strategies for bioengineering thermostable proteins for medical and industrial purposes. Interim findings point to new design paradigms….

The contribution is available here and the high resolution pdf can be downloaded from the publications page.

TEACHING

Chemical Reactivity (ENS) ::

Cutting Edge Research in Chemical Reactivity (Web Site Vive la Cinétique)

RCTF 2015-present ::

1. Multi-scale modelling of biophysical processes. S. Soquin-Mora

2. Protein in silico. Modelling cell-like environments. F. Sterpone

BLOG IN SCIENCE ::

Ed-Yong. Science writings from Ed Yong.

X-proteins. When proteins live in extreme conditions (by F. Sterpone and the Thermos crew)

Water in Biology. Role of water in biological processes (by P. Ball)

Condensed Concepts. Emerging phenomena in condesed phases of matter (by R.H. McKenzie, Univ. of Qeensland, Australia).

Macromolecular Modeling. Discussions on modelling of structure, function and interactions of biomolecules (by RosettaDesginGroup)

https://sites.google.com/site/sterponefabio/home/vlcsnap-2014-02-07-08h45m34s199.png

FUNDING





>> Be hot, be cool. Life on Earth exhibits an amazing adaptive capacity.

Organisms can thrive in extremes conditions, from glacial water (0°C) to hot springs (100°C). An amazing view of this adaptation is given by the color gradient in Yellowstone’s hot springs. A puzzling question is how organisms can fight the degrading action of temperature, and more, how they optimize the chemical processes of their metabolism as function of the living temperature. To answer this, we need to go down to proteins, soft-matter entities, that make life in action. Some interesting aspects are discussed in two twin-papers just out. Enjoy them! https://lnkd.in/d7EMs4r and https://lnkd.in/dEnhVjZ.