13 rue Pierre et Marie Curie, 75005 Paris, FR
office 332
tel  :: +33-1-58415169
fax :: +33-1-58415020
email :: fabio.sterpone [at] ibpc.fr

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


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

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 quantum/classical to coarse-graining/nanoscale descriptions. 

1. 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.
2. 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.
3. G. Stirnemann, F. Sterpone, "Mechanics of Protein Adaptation to High Temperatures", J. Phys. Chem. Lett.,(2017), 8, 5884–5890. 
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.


>> A nice highlight of a recent computational BigChallenge we participated to at the machine Occigen@CINES, here.

>> Question is: in order to be stable at high temperature, a thermophilic protein does it require also to be mechanically resistant? In some sense, the idea to be more rigid than the mesophilic homologous is directly deduced by the fact the thermopiles generally lack activity at ambient conditions where their mesophilic homologues work. But not necessarily the functional rigidity, if any, corresponds to mechanical resistance against a pulling force. Enjoy ''Mechanics of Protein Adaptation to High Temperatures", J. Phys. Chem. Lett.,(2017), [here], and the editorial spotlight [here].

>> Lindemann criterion states that a solid melts when the local fluctuations overpass a critical fraction of the lattice space, e.g. 20%. Can the melting of a protein resembles what happen in solids? The answer is yes. Read our work where we have combined neutron scattering and sophisticated in silico calculations: ''Critical structural fluctuations of proteins upon thermal unfolding challenge the Lindemann criterion'', PNAS (2017), [here]. A nice highlight is just out in the PhysOrg web site and provided by ILL read here.

>> How does water HB network reorganise? Using graph theory and clustering we explore the configurational states of water HB network embedded in a protein matrix, and correlate the increase of entropy with the protein dynamical transition. Enjoy the work ''Configurational Disorder of Water Hydrogen-Bond Network at the Protein Dynamical Transition'' here. The code developed to perform the clustering of the HB network state is publicly available here.

>> Award Young Researcher:: Marina Katava received the award at the last GGMM meeting 2017 in Reims (FR). It was recognised her work on protein's stability and functionality in high temperature regime that she accomplished during the PhD. Congratulations!

>> Temperature and large scale motions: by combining neutron scattering spin echo experiments with MD simulations we have explored how large scale inter-domains motions in Lactate Dehydrogenase get activated by temperature "Thermal activation of ‘allosteric-like’ large-scale motions in a eukaryotic Lactate Dehydrogenase", Sci.Reports (2016) [here]. The work has been highlighter in the Annual Report of MLZ Neutron Scattering facility [here].

>>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 environmentsin 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.


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

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)