Fabio Cecconi - Academia.edu (original) (raw)

Papers by Fabio Cecconi

European Biophysics Journal

The folding properties of wild type and mutants of domain C5 from cardiac myosin binding protein ... more The folding properties of wild type and mutants of domain C5 from cardiac myosin binding protein C have been investigated via molecular dynamics simulations within the framework of a native-centric and coarse-grained model. The relevance of a mutation has been assessed through the shift in the unfolding temperature, the change in the unfolding rate it determines and Phi-values analysis. In a previous paper (Guardiani et al. Biophys J 94:1403-1411, 2008), we performed Kinetic simulations on native contact formation revealing an entropy-driven folding pathway originating near the FG and DE loops. This folding mechanism allowed also a possible interpretation of the molecular impact of the three mutations, Arg14His, Arg28His and Asn115Lys involved in the Familial Hypertrophic Cardiomyopathy. Here we extend that analysis by enriching the mutant pool and we identify a correlation between unfolding rates and the number of native contacts retained in the transition state.

The availability of a large amount of experimental data makes the Pin1 WW domain an ideal benchma... more The availability of a large amount of experimental data makes the Pin1 WW domain an ideal benchmark to test computational methods. The purpose of the present work is to identify the kinetic bottlenecks of the folding/unfolding pathway through Molecular Dynamics simulations. In this paper, the rst of the series, we use the Sorenson/Head-Gordon model, based on the hydrophobicity properties of

The present paper is the second of a series in which we perform molecular dynamics simulations on... more The present paper is the second of a series in which we perform molecular dynamics simulations on the WW domain of Pin1 protein. The aim of the work is the reconstruction of the folding/unfolding pathway with a special interest for the kinetic bottlenecks. In the rst paper of the series we showed that unfolding simulations using the Sorenson/Head-Gordon (SHG) model

The journal of physical chemistry. B, Jan 13, 2015

In nanopore sensing experiments the properties of molecules are probed by the variation of ionic ... more In nanopore sensing experiments the properties of molecules are probed by the variation of ionic currents flowing through the nanopore. In this context, the electronic properties and the single-layer thickness of graphene constitute a major advantage for molecule characterization. Here we analyze the translocation pathway of the thioredoxin protein across a graphene nanopore, and the related ionic currents, by integrating two non-equilibrium molecular dynamics methods with a bioinformatic structural analysis. To obtain a qualitative picture of the translocation process and to identify salient features we performed unsupervised structural clustering on translocation conformations. This allowed us to identify some specific and robust translocation intermediates, characterized by significantly different ionic current flows. We found that the ion current strictly anticorrelates with the amount of pore occupancy by thioredoxin residues, providing a putative explanation of the multilevel ...

Physical review. E, Statistical, nonlinear, and soft matter physics, 2014

We study the asymptotic and preasymptotic diffusive properties of Brownian particles in channels ... more We study the asymptotic and preasymptotic diffusive properties of Brownian particles in channels whose section varies periodically in space. The effective diffusion coefficient D(eff) is numerically determined by the asymptotic behavior of the root mean square displacement in different geometries, considering even cases of steep variations of the channel boundaries. Moreover, we compared the numerical results to the predictions from the various corrections proposed in the literature to the well known Fick-Jacobs approximation. Building an effective one-dimensional equation for the longitudinal diffusion, we obtain an approximation for the effective diffusion coefficient. Such a result goes beyond a perturbation approach, and it is in good agreement with the actual values obtained by the numerical simulations. We discuss also the preasymptotic diffusion which is observed up to a crossover time whose value, in the presence of strong spatial variation of the channel cross section, can ...

Nanofluidics, thanks to the recent progress in the fabrication of micro and nanodevices, has beco... more Nanofluidics, thanks to the recent progress in the fabrication of micro and nanodevices, has become an intense research field. Confined fluids in nanoscale geometries exhibit physical behaviors that, in several cases, largely differ from macroscale dynamics. The crucial differences are: i) in nanoscale systems the usual mathematical description for continuum fluid dynamics (Navier-Stokes equation), often fails to reproduce the correct fluid dynamics behavior and ii) in a number of crucial applications the focus is on the motion of a single macromolecule. These occurrences naturally call for an atomistic description of the whole system, which however remains currently limited to relatively small systems (tens of nm simulated for hundreds of ns). The simulation of the fluid motion at nanoscale is here addressed via a recent developed mesoscale approach. In particular the flow of an electrolyte through a nano channel is analyzed. The system represent an experimentally well characterized solid-state nanopore employed for DNA and protein translocation. The simulations are aimed at estimating the effect of DNA translocation on mass and charge flow rate potentially shedding light on the molecular mechanism behind recent experimental observations.

Intermediate resolution spectroscopic observations provide a window into the immediate environmen... more Intermediate resolution spectroscopic observations provide a window into the immediate environment of young stars. In particular such studies have yielded much new information regarding outflow activity and binarity. Using spectroscopy one can investigate the kinematics and excitation conditions of jets close to where they are launched and resolve close binaries. The primary constraint to the use of spectroscopy in this manner is the maximum spatial resolution achievable. Observers are all the time aiming to improve angular resolution and overcome the limiting effects of the Earth's atmosphere. This is where the technique of spectro-astrometry comes to the fore. The spectro-astrometric technique, which allows the user to recover sub-seeing spatial information from a simple spectrum has been applied to many interesting problems. For example spectro-astrometry has been used to discover that brown dwarfs can drive outflows. In this review of spectro-astrometry we shall discuss the technique beginning with a revision of angular resolution and astrometry. The limitations of the technique are described and the uses to which it has been put to date are extensively discussed.

EPL (Europhysics Letters), 2014

Note that the author(s) has the following rights: -immediately after publication, to use all or p... more Note that the author(s) has the following rights: -immediately after publication, to use all or part of the article without revision or modification, including the EPLAformatted version, for personal compilations and use only; -no sooner than 12 months from the date of first publication, to include the accepted manuscript (all or part), but not the EPLA-formatted version, on institute repositories or third-party websites provided a link to the online EPL abstract or EPL homepage is included.

PHYSICAL REVIEW E, 1998

A coupled-map lattice showing complex behavior in the presence of a fully negative Lyapunov spect... more A coupled-map lattice showing complex behavior in the presence of a fully negative Lyapunov spectrum is considered. A dynamical phase transition from ''frozen'' disorder to chaoticlike evolution upon changing diffusive coupling is studied in detail. Various indicators provide a coherent description of the scenario: the existence of a finite transition region characterized by an irregular alternancy of periodic and chaotic evolution.

JOURNAL OF PHYSICS A-MATHEMATICAL AND GENERAL, 1999

In this work we present a theoretical and numerical study of the behaviour of the maximum Lyapuno... more In this work we present a theoretical and numerical study of the behaviour of the maximum Lyapunov exponent in products of random tridiagonal matrices in the limit of small coupling and small fluctuations. Such a problem is directly motivated by the investigation of coupled-map lattices in a regime where the chaotic properties are quite robust and yet a complete understanding has still not been reached. We derive some approximate analytic expressions by introducing a suitable continuous-time formulation of the evolution equation. As a first result, we show that the perturbation of the Lyapunov exponent due to the coupling depends only on a single scaling parameter which, in the case of strictly positive multipliers, is the ratio of the coupling strength with the variance of local multipliers. An explicit expression for the Lyapunov exponent is obtained by mapping the original problem onto a chain of nonlinear Langevin equations, which are eventually reduced to a single stochastic equation. The probability distribution of this dynamical equation provides an excellent description for the behaviour of the Lyapunov exponent. Finally, multipliers with random signs are also considered, finding that the Lyapunov exponent again depends on a single scaling parameter, which, however, has a different expression.

PHYSICS LETTERS A, 2001

A synchronization mechanism driven by annealed noise is studied for two replicas of a coupled-map... more A synchronization mechanism driven by annealed noise is studied for two replicas of a coupled-map lattice which exhibits stable chaos (SC), i.e. irregular behavior despite a negative Lyapunov spectrum. We show that the observed synchronization transition, on changing the strength of the stochastic coupling between replicas, belongs to the directed percolation universality class. This result is consistent with the behavior of chaotic deterministic cellular automata (DCA), supporting the equivalence Ansatz between SC models and DCA. The coupling threshold above which the two system replicas synchronize is strictly related to the propagation velocity of perturbations in the system.

Noise and Fluctuations in Biological, Biophysical, and Biomedical Systems, 2007

ABSTRACT Three mutations of domain C5 of Myosin Binding Protein C are involved in Familial Hypert... more ABSTRACT Three mutations of domain C5 of Myosin Binding Protein C are involved in Familial Hypertrophic Cardiomyopathy. We assess their impact through Molecular Dynamics simulations within the framework of a native-centric coarse-grained model. We characterize the clinical relevance of a mutation by: the extent of temperature shift it induces in the unfolding transition, the increase of the kinetic unfolding rates with respect to the wild type, and by φ-value analysis. Further analysis of folding stages based on the evolution of native contact probabilities reveals an entropy-driven pathway originating in the protein region close to Res115 and ending up in the area of Res28. The mutation of the former residue thus appears to be responsible for an early interruption of the folding process, leaving the protein largely unstructured and yielding a serious impairment of cardiac function. Mut28, on the contrary, thwarts a late stage of folding when the protein is almost completely native-like, leading to a mild phenotype. A bio-informatic analisys of the long and destabilizing CD loop finally shows an excess of negative charge and a low hydrophobicity indicating a possible classification as a natively unfolded sequence. Accordingly, the folding mechanism is suggested to be coupled with binding with a specific ligand.

Current Bioinformatics, 2010

The theoretical prediction of protein structures has become a field of increasing importance in b... more The theoretical prediction of protein structures has become a field of increasing importance in both biology and physics. Reliable prediction methods in fact, would spare time consuming experimental X-ray and NMR techniques and they would represent a challenge for computational protein modeling as well. The well known limitations of all-atom models call for the development of coarse-grained protein descriptions including a minimal number of protein-like features, while being capable of mimicking the essence of protein folding mechanisms. In this paper we review the most important classes of coarse-grained protein models in order of increasing complexity, starting from (over simplified) binary models, to models with one or two reaction centers per residue. We discuss how, despite their simplification, coarsegrained models constitute a viable approach to structure prediction and they shed light on many aspects of protein-folding problem.

Lecture Notes in Physics, 2008

Physical Review E, 2000

We present the results of analytical studies of a one-dimensional nonlocal and nonlinear diffusio... more We present the results of analytical studies of a one-dimensional nonlocal and nonlinear diffusion equation describing nonequilibrium processes ranging from aggregation phenomena to the cooperation of individuals. On tuning the initial conditions, a dynamical transition with a universal scaling behavior is observed between two different asymptotic (in time) solutions. The scaling behavior at the transition is also obtained in a self-organized manner, independent of the initial conditions, on temporally evolving the diffusion equation subjected to a mirror symmetry transformation.

Physica D: Nonlinear Phenomena, 2003

We investigate the origin of diffusion in non-chaotic systems. As an example, we consider 1D map ... more We investigate the origin of diffusion in non-chaotic systems. As an example, we consider 1D map models whose slope is everywhere 1 (therefore the Lyapunov exponent is zero) but with random quenched discontinuities and quasi-periodic forcing. The models are constructed as non-chaotic approximations of chaotic maps showing deterministic diffusion, and represent one-dimensional versions of a Lorentz gas with polygonal obstacles (e.g., the Ehrenfest wind-tree model). In particular, a simple construction shows that these maps define non-chaotic billiards in space-time. The models exhibit, in a wide range of the parameters, the same diffusive behavior of the corresponding chaotic versions. We present evidence of two sufficient ingredients for diffusive behavior in one-dimensional, non-chaotic systems: (i) a finite size, algebraic instability mechanism; (ii) a mechanism that suppresses periodic orbits.

The Journal of Physical Chemistry B, 2012

We present a computational study on the driven transport of the Maltose Binding Protein (MBP) acr... more We present a computational study on the driven transport of the Maltose Binding Protein (MBP) across nanochannels in the framework of coarse-grained modeling. The work is motivated by recent experiments on voltage-driven transport of MBP across nanopores exploring the influence of denaturation on translocation pathways. Our simplified approach allows a statistical mechanical interpretation of the process which may be convenient also to the experiments. Specifically, we identify and characterize short and long channel blockades, associated to the translocation of denaturated and folded MBP conformations, respectively. We show that long blockades are related to long stall events where MBP undergoes specific and reproducible structural rearrangements. To clarify the origin of the stalls, the stick-and-slip translocation is compared to mechanical unfolding pathways obtained via steered molecular dynamics. This comparison clearly shows the translocation pathway to significantly differ from free-space unfolding dynamics and strongly suggests that stalling events are preferentially determined by the MBP regions with higher density of long-range native interactions. This result might constitute a possible criterion to predict a priori some statistical features of protein translocation from the structural analysis.