arXiv subjects

Francesco Piazza

Publications and source records attributed to Francesco Piazza.

102 records · Page 6Linked to original sources

arXiv2008

Temperature dependence of normal mode reconstructions of protein dynamics

Normal mode analysis is a widely used technique for reconstructing conformational changes of proteins from the knowledge of native structures. In this Letter, we investigate to what extent normal modes capture the salient features of the dynamics over a range of temperatures from close to T = 0 to above unfolding. We show that on the one hand, the use of normal modes at physiological temperatures is justified provided proteins are cooperative. On the other hand, it is imperative to consider several modes in order to eliminate the unpredictable temperature dependence of single- mode contributions to the protein fluctuations.

cond-mat.stat-mech↗

arXiv2008

Discrete breathers in protein structures

Recently, using a numerical surface cooling approach, we have shown that highly energetic discrete breathers (DB) can form in the stiffest parts of nonlinear network models of large protein structures. In the present study, using an analytical approach, we extend our previous results to low-energy discrete breathers as well as to smaller proteins We confirm and further scrutinize the striking site selectiveness of energy localisation in the presence of spatial disorder. In particular, we find that, as a sheer consequence of disorder, a non-zero energy gap for exciting a DB at a given site either exists or not. Remarkably, in the former case, the gaps arise as result of the impossibility of exciting small-amplitude modes in the first place. On the contrary, in the latter case, a small subset of linear edge modes act as accumulation points, whereby DBs can be continued to arbitrary small energies, while unavoidably approaching one of such normal modes. In particular, the case of the edge mode seems peculiar, its dispersion relation being simple and little system-dependent. Concerning the structure-dynamics relationship, we find that the regions of protein structures where DBs form easily (zero or small gaps) are unfailingly the most highly connected ones, also characterized by weak local clustering. Remarkably, a systematic analysis on a large database of enzyme structures reveals that amino-acid residues involved in enzymatic activity tend to be located in such regions. This finding reinforces the idea that localised modes of nonlinear origin may play an important biological role, e.g. by providing a ready channel for energy storage and/or contributing to lower energy barriers of chemical reactions.

q-bio.BM↗

arXiv2007

Discrete breathers in nonlinear network models of proteins

We introduce a topology-based nonlinear network model of protein dynamics with the aim of investigating the interplay of spatial disorder and nonlinearity. We show that spontaneous localization of energy occurs generically and is a site-dependent process. Localized modes of nonlinear origin form spontaneously in the stiffest parts of the structure and display site-dependent activation energies. Our results provide a straightforward way for understanding the recently discovered link between protein local stiffness and enzymatic activity. They strongly suggest that nonlinear phenomena may play an important role in enzyme function, allowing for energy storage during the catalytic process.

q-bio.BM↗

arXiv2007

Diffusion-limited unbinding of small peptides from PDZ domains

PDZ domains are typical examples of binding motifs mediating the formation of protein-protein assemblies in many different cells. A quantitative characterization of the mechanisms intertwining structure, chemistry and dynamics with the PDZ function represent a challenge in molecular biology. Here we investigated the influence of native state topology on the thermodynamics and the dissociation kinetics for a complex PDZ-peptide via Molecular Dynamics simulations based on a coarse-grained description of PDZ domains. Our native-centric approach neglects chemical details but incorporates the basic structural information to reproduce the protein functional dynamics as it couples to the binding. We found that at physiological temperatures the unbinding of a peptide from the PDZ domain becomes increasingly diffusive rather than thermally activated, as a consequence of the significant reduction of the free energy barrier with temperature. In turn, this results in a significant slowing down of the process of two orders of magnitude with respect to the conventional Arrhenius extrapolation from low temperature calculations. Finally, a detailed analysis of a typical unbinding event based on the rupture times of single peptide-PDZ contacts allows to shed further light on the dissociation mechanism and to elaborate a coherent picture of the relation between function and dynamics in PDZ domains.

physics.bio-ph↗

arXiv2006

On the origin of the Boson peak in globular proteins

We study the Boson Peak phenomenology experimentally observed in globular proteins by means of elastic network models. These models are suitable for an analytic treatment in the framework of Euclidean Random Matrix theory, whose predictions can be numerically tested on real proteins structures. We find that the emergence of the Boson Peak is strictly related to an intrinsic mechanical instability of the protein, in close similarity to what is thought to happen in glasses. The biological implications of this conclusion are also discussed by focusing on a representative case study.

cond-mat.soft↗

arXiv2006

The Glass-like Structure of Globular Proteins and the Boson Peak

Vibrational spectra of proteins and topologically disordered solids display a common anomaly at low frequencies, known as Boson peak. We show that such feature in globular proteins can be deciphered in terms of an energy landscape picture, as it is for glassy systems. Exploiting the tools of Euclidean random matrix theory, we clarify the physical origin of such anomaly in terms of a mechanical instability of the system. As a natural explanation, we argue that such instability is relevant for proteins in order for their molecular functions to be optimally rooted in their structures.

cond-mat.soft↗

arXiv2005

Slow energy relaxation of macromolecules and nano-clusters in solution

Many systems in the realm of nanophysics from both the living and inorganic world display slow relaxation kinetics of energy fluctuations. In this paper we propose a general explanation for such phenomenon, based on the effects of interactions with the solvent. Within a simple harmonic model of the system fluctuations, we demonstrate that the inhomogeneity of coupling to the solvent of the bulk and surface atoms suffices to generate a complex spectrum of decay rates. We show for Myoglobin and for a metal nano-cluster that the result is a complex, non-exponential relaxation dynamics.

cond-mat.stat-mech↗

arXiv2005

Functional Dynamics of PDZ Binding Domains: A Normal Mode Analysis

PDZ (Post-synaptic density-95/discs large/zonula occludens-1) domains are relatively small (80 to 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 of communication between distant regions of the protein, in agreement with recent Nuclear Magnetic Resonance (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/unbonding events.

q-bio.BM↗

arXiv2005

Statistical analysis of simple repeats in the human genome

The human genome contains repetitive DNA at different level of sequence length, number and dispersion. Highly repetitive DNA is particularly rich in homo-- and di--nucleotide repeats, while middle repetitive DNA is rich of families of interspersed, mobile elements hundreds of base pairs (bp) long, among which the Alu families. A link between homo- and di-polymeric tracts and mobile elements has been recently highlighted. In particular, the mobility of Alu repeats, which form 10% of the human genome, has been correlated with the length of poly(A) tracts located at one end of the Alu. These tracts have a rigid and non-bendable structure and have an inhibitory effect on nucleosomes, which normally compact the DNA. We performed a statistical analysis of the genome-wide distribution of lengths and inter--tract separations of poly(X) and poly(XY) tracts in the human genome. Our study shows that in humans the length distributions of these sequences reflect the dynamics of their expansion and DNA replication. By means of general tools from linguistics, we show that the latter play the role of highly-significant content-bearing terms in the DNA text. Furthermore, we find that such tracts are positioned in a non-random fashion, with an apparent periodicity of 150 bases. This allows us to extend the link between repetitive, highly mobile elements such as Alus and low-complexity words in human DNA. More precisely, we show that Alus are sources of poly(X) tracts, which in turn affect in a subtle way the combination and diversification of gene expression and the fixation of multigene families.

q-bio.GN↗

arXiv2005

Stretched--exponential relaxation in arrays of coupled rotators

We consider the non--equilibrium dynamics of a chain of classical rotators coupled at its edges to an external reservoir at zero temperature. We find that the energy is released in a strongly discontinuous fashion, with sudden jumps alternated with long stretches during which dissipation is extremely weak. The jumps mark the disappearance of strongly localized structures, akin to the rotobreather solutions of the Hamiltonian model, which act as insulating boundaries of a hot central core. As a result of this complex kinetics, the ensemble--averaged energy follows a stretched exponential law until a residual pseudo--stationary state is attained, where the hot core has reduced to a single localized object. We give a statistical description of the relaxation pathway and connect it to the properties of return periods of rare events in correlated time series. This approach sheds some light into the microscopic mechanism underlying the slow dynamics of the system. Finally, we show that the stretched exponential law remains unaltered in the presence of isotopic disorder.

cond-mat.other↗

arXiv2004

The Anti-FPU Problem

We present a detailed analysis of the modulational instability of the zone-boundary mode for one and higher-dimensional Fermi-Pasta-Ulam (FPU) lattices. Following this instability, a process of relaxation to equipartition takes place, which we have called the Anti-FPU problem because the energy is initially fed into the highest frequency part of the spectrum, at variance with the original FPU problem (low frequency excitations of the lattice). This process leads to the formation of chaotic breathers in both one and two dimensions. Finally, the system relaxes to energy equipartition on time scales which increase as the energy density is decreased. We show that breathers formed when cooling the lattice at the edges, starting from a random initial state, bear strong qualitative similarities with chaotic breathers.

nlin.PS↗

arXiv2002

A quantum perturbative pair distribution for determining interatomic potentials from extended X-ray absorption spectroscopy

In this paper we develop a technique for determining interatomic potentials in materials in the quantum regime from single--shell Extended X-ray Absorption Spectroscopy (EXAFS) spectra. We introduce a pair distribution function, based on ordinary quantum time--independent perturbation theory. In the proposed scheme, the model potential parameters enter the distribution through a fourth--order Taylor expansion of the potential, and are directly refined in the fit of the model signal to the experimental spectrum. We discuss in general the validity of our theoretical framework, namely the quantum regime and perturbative treatment, and work out a simple tool for monitoring the sensitivity of our theory in determining lattice anharmonicities based on the statistical $F$--test. As an example, we apply our formalism to an EXAFS spectrum at the Ag K--edge of AgI at T=77 K. We determine the Ag--I potential parameters and find good agreement with previous studies.

cond-mat.mtrl-sci↗