Biomedical subjects

Fabio Cecconi

Publications and source records attributed to Fabio Cecconi.

12 recordsLinked to original sources

PubMed2006

Transport of a heated granular gas in a washboard potential.

We study numerically the motion of a one dimensional array of Brownian particles in a washboard potential, driven by an external stochastic force and interacting via short range repulsive forces. In particular, we investigate the role of instantaneous elastic and inelastic collisions on the system dynamics and transport. The system displays a locked regime, where particles may move only via activated processes and a running regime where particles drift along the direction of the applied field. By tuning the value of the friction parameter controlling the Brownian motion we explore both the overdamped dynamics and the underdamped dynamics. In the two regimes we considered the mobility and the diffusivity of the system as functions of the tilt and other relevant control parameters such as coefficient of restitution, particle size, and total number of particles. We find that while in the overdamped regime the results for the interacting systems present similarities with the known noninteracting case, in the underdamped regime the inelastic collisions determine a rich variety of behaviors among which is an unexpected enhancement of the inelastic diffusion.

Algorithms↗

PubMed2006

Testing simplified proteins models of the hPin1 WW domain.

The WW domain of the human Pin1 protein for its simple topology and large amount of experimental data is an ideal candidate to assess theoretical approaches to protein folding. The purpose of this work is to compare the reliability of the chemically based Sorenson/Head-Gordon (SHG) model and a standard native centric model in reproducing, through molecular dynamics simulations, some of the well known features of the folding transition of this small domain. Our results show that the Gō model correctly reproduces the cooperative, two-state, folding mechanism of the WW-domain, while the SHG model predicts a transition occurring in two stages: a collapse, followed by a structural rearrangement. The lack of a cooperative folding in the SHG simulations appears to be related to the nonfunnel shape of the energy landscape featuring a partitioning of the native valley in subbasins corresponding to different chain chiralities. However, the SHG approach remains more reliable in estimating the phi-values with respect to Gō-like description. This may suggest that the WW-domain folding process is stirred by energetic and topological factors as well, and it highlights the better suitability of chemically based models in simulating mutations.

Computer Simulation↗

PubMed2006

Inelastic Takahashi hard-rod gas.

We study a one-dimensional fluid of hard rods interacting with each other via binary inelastic collisions and a short-ranged square-well potential. Upon tuning the depth and the sign of the well, we investigate the interplay between dissipation and cohesive or repulsive forces. Molecular-dynamics simulations of the cooling regime indicate that the presence of this simple interparticle interaction is sufficient to significantly modify the energy dissipation rates expected by Haff's law for the free cooling. The simplicity of the model makes it amenable to an analytical approach based on the Boltzmann-Enskog transport equation which allows deriving the behavior of the granular temperature. Furthermore, in the elastic limit, the model can be solved exactly to provide a full thermodynamic description. A meaningful theoretical approximation explaining the properties of the inelastic system in interaction with a thermal bath can be directly extrapolated from the properties of the corresponding elastic system, upon a proper redefinition of the relevant observables. Simulation results both in the cooling and driven regimes can be fairly interpreted according to our theoretical approach and compare rather well to our predictions.

Journal Article↗

PubMed2005

Functional dynamics of PDZ binding domains: a normal-mode analysis.

Postsynaptic density-95/disks large/zonula occludens-1 (PDZ) domains are relatively small (80-120 residues) protein binding modules central in the organization of receptor clusters and in the association of cellular proteins. Their main function is to bind C-terminals of selected proteins that are recognized through specific amino acids in their carboxyl end. Binding is associated with a deformation of the PDZ native structure and is responsible for dynamical changes in regions not in direct contact with the target. We investigate how this deformation is related to the harmonic dynamics of the PDZ structure and show that one low-frequency collective normal mode, characterized by the concerted movements of different secondary structures, is involved in the binding process. Our results suggest that even minimal structural changes are responsible for communication between distant regions of the protein, in agreement with recent NMR experiments. Thus, PDZ domains are a very clear example of how collective normal modes are able to characterize the relation between function and dynamics of proteins, and to provide indications on the precursors of binding/unbinding events.

Adenosine Triphosphate↗

PubMed2004

Analysis of PIN1 WW domain through a simple statistical mechanics model.

We have applied a simple statistical mechanics Go-like model to the analysis of the PIN1 WW domain, resorting to mean field and Monte Carlo techniques to characterize its thermodynamics, and comparing the results with the wealth of available experimental data. PIN1 WW domain is a 39-residue protein fragment which folds on an antiparallel beta-sheet, thus representing an interesting model system to study the behavior of these secondary structure elements. Results show that the model correctly reproduces the two-state behavior of the protein, and also the trends of the experimental phi(T) values. Moreover, there is a good agreement between Monte Carlo results and the mean field ones, which can be obtained with a substantially smaller computational effort.

Models, Statistical↗

PubMed2004

Inelastic hard rods in a periodic potential.

A simple model of inelastic hard rods subject to a one-dimensional array of identical wells is introduced. The energy loss due to inelastic collisions is balanced by the work supplied by an external stochastic heat bath. We explore the effect of the spatial nonuniformity on the steady states of the system. The spatial variations of the density, granular temperature, and pressure induced by the gradient of the external potential are investigated and compared with the analogous variations in an elastic system. Finally, we study the clustering process by considering the relaxation of the system starting from a uniform homogeneous state.

Journal Article↗

PubMed2004

Topological thermal instability and length of proteins.

We present an analysis of the effects of global topology on the structural stability of folded proteins in thermal equilibrium with a heat bath. For a large class of single domain proteins, we computed the harmonic spectrum within the Gaussian Network Model (GNM) and determined their spectral dimension, a parameter describing the low frequency behavior of the density of modes. We found a surprisingly strong correlation between the spectral dimension and the number of amino acids in the protein. Considering that larger spectral dimension values relate to more topologically compact folded states, our results indicate that, for a given temperature and length of protein, the folded structure corresponds to a less compact folding, one compatible with thermodynamic stability.

Amino Acids↗

PubMed2004

Minimal stochastic model for Fermi's acceleration.

We introduce a simple stochastic system able to generate anomalous diffusion for both position and velocity. The model represents a viable description of the Fermi's acceleration mechanism and it is amenable to analytical treatment through a linear Boltzmann equation. The asymptotic probability distribution functions for velocity and position are explicitly derived. The diffusion process is highly non-Gaussian and the time growth of moments is characterized by only two exponents nu(x) and nu(v). The diffusion process is anomalous (non-Gaussian) but with a defined scaling property, i.e., P(|r|,t)=1/t(nu(x))Fx(|r|/t(nu(x))) and similarly for velocity.

Journal Article↗

PubMed2004

Fluid-like behavior of a one-dimensional granular gas.

We study the properties of a one-dimensional (1D) granular gas consisting of N hard rods on a line of length L (with periodic boundary conditions). The particles collide inelastically and are fluidized by a heat bath at temperature Tb and viscosity gamma. The analysis is supported by molecular dynamics simulations. The average properties of the system are first discussed, focusing on the relations between granular temperature Tg=mv2, kinetic pressure, and density rho=N/L. Thereafter, we consider the fluctuations around the average behavior obtaining a slightly non-Gaussian behavior of the velocity distributions and a spatially correlated velocity field; the density field displays clustering: this is reflected in the structure factor which has a peak in the k approximately 0 region suggesting an analogy between inelastic hard core interactions and an effective attractive potential. Finally, we study the transport properties, showing the typical subdiffusive behavior of 1D stochastically driven systems, i.e., approximately Dt(1/2), where D for the inelastic fluid is larger than the elastic case. This is directly related to the peak of the structure factor at small wave vectors.

Journal Article↗

PubMed2003

Noise activated granular dynamics.

We study the behavior of two particles moving in a bistable potential, colliding inelastically with each other and driven by a stochastic heat bath. The system has the tendency to clusterize, placing the particles in the same well at low drivings, and to fill all of the available space at high temperatures. We show that the hopping over the potential barrier occurs following the Arrhenius rate, where the heat bath temperature is replaced by the granular temperature. Moreover, within the clusterized "phase" one encounters two different scenarios: For moderate inelasticity, the jumps from one well to the other involve one particle at a time, whereas for strong inelasticity the two particles hop simultaneously.

Journal Article↗

PubMed2002

Diffusion, peer pressure, and tailed distributions.

We present a general, physically motivated nonlinear and nonlocal advection equation in which the diffusion of interacting random walkers competes with a local drift arising from a kind of peer pressure. We show, using a mapping to an integrable dynamical system, that on varying a parameter the steady-state behavior undergoes a transition from the standard diffusive behavior to a localized stationary state characterized by a tailed distribution. Finally, we show that recent empirical laws on economic growth can be explained as a collective phenomenon due to peer pressure interaction.

Economics↗

PubMed2002

Crucial stages of protein folding through a solvable model: predicting target sites for enzyme-inhibiting drugs.

An exactly solvable model based on the topology of a protein native state is applied to identify bottlenecks and key sites for the folding of human immunodeficiency virus type 1 (HIV-1) protease. The predicted sites are found to correlate well with clinical data on resistance to Food and Drug Administration-approved drugs. It has been observed that the effects of drug therapy are to induce multiple mutations on the protease. The sites where such mutations occur correlate well with those involved in folding bottlenecks identified through the deterministic procedure proposed in this study. The high statistical significance of the observed correlations suggests that the approach may be promisingly used in conjunction with traditional techniques to identify candidate locations for drug attacks.

Amino Acids↗