arXiv subjects

Amos Maritan

Publications and source records attributed to Amos Maritan.

At least 145 records · Page 8Linked to original sources

arXiv2003

Scaling and universality in ontogenetic growth

Recently, West et al. claimed to derive a general quantitative model based on fundamental principles for the allocation of metabolic energy between maintenance of existing tissue and the production of new biomass, and in addition claimed to derive a single, parameterless universal curve that describes the growth of many species. They further claimed that their model of the 3/4 exponent for the allometric scaling of metabolism provides a novel version of the growth equations and use the goodness of fit of growth-curve data to these equations as support of this interpretation. Here, we show that the universal curve arises from general considerations that are independent of the specific allometric model used and that the data do not distinguish between the 3/4 or the 2/3 exponent for the metabolic rate mass scaling.

cond-mat↗

arXiv2003

From polymers to proteins -- novel phases of short compact tubes

A framework is presented for understanding the common character of proteins. Proteins are linear chain molecules. However, the simple model of a polymer viewed as spheres tethered together does not account for many of the observed characteristics of protein structures. The authors show here that proteins may be regarded as tubes of nonzero thickness. This approach allows one to bridge the conventional compact polymer phase with a novel phase employed by Nature to house biomolecular structures. The continuum description of a tube (or a sheet) of arbitrary thickness entails using appropriately chosen many-body interactions rather than two-body interactions. The authors suggest that the structures of folded proteins are selected based on geometrical considerations and are poised at the edge of compaction, thus accounting for their versatility and flexibility. This approach also offers an explanation for why helices and sheets are the building blocks of protein structures.

cond-mat.stat-mech↗

arXiv2002

Effects of Pore Walls and Randomness on Phase Transitions in Porous Media

We study spin models within the mean field approximation to elucidate the topology of the phase diagrams of systems modeling the liquid-vapor transition and the separation of He$^3$--He$^4$ mixtures in periodic porous media. These topologies are found to be identical to those of the corresponding random field and random anisotropy spin systems with a bimodal distribution of the randomness. Our results suggest that the presence of walls (periodic or otherwise) are a key factor determining the nature of the phase diagram in porous media.

cond-mat.stat-mech↗

arXiv2002

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 HIV-1 Protease. The predicted sites are found to correlate well with clinical data on resistance to FDA-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.

cond-mat.stat-mech↗

arXiv2002

Elastic properties of proteins: insight on the folding process and evolutionary selection of native structures

We carry out a theoretical study of the vibrational and relaxation properties of naturally-occurring proteins with the purpose of characterizing both the folding and equilibrium thermodynamics. By means of a suitable model we provide a full characterization of the spectrum and eigenmodes of vibration at various temperatures by merely exploiting the knowledge of the protein native structure. It is shown that the rate at which perturbations decay at the folding transition correlates well with experimental folding rates. This validation is carried out on a list of about 30 two-state folders. Furthermore, the qualitative analysis of residues mean square displacements (shown to accurately reproduce crystallographic data) provides a reliable and statistically accurate method to identify crucial folding sites/contacts. This novel strategy is validated against clinical data for HIV-1 Protease. Finally, we compare the spectra and eigenmodes of vibration of natural proteins against randomly-generated compact structures and regular random graphs. The comparison reveals a distinctive enhanced flexibility of natural structures accompanied by slow relaxation times at the folding temperature. The fact that these properties are intimately connected to the presence and assembly of secondary motifs hints at the special criteria adopted by evolution in the selection of viable folds.

cond-mat.stat-mech↗

arXiv2002

Diffusion, peer pressure and tailed distributions

We present a general, physically motivated non-linear and non-local 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 behaviour 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.

cond-mat.stat-mech↗

arXiv2002

Prediction of Protein Secondary Structures From Conformational Biases

We use LINUS, a procedure developed by Srinivasan and Rose, to provide a physical interpretation of and to predict the secondary structures of proteins. The secondary structure type at a given site is identified by the largest conformational bias during short time simulations. We examine the rate of successful prediction as a function of temperature and the interaction window. At high temperatures, there is a large propensity for the establishment of $β$-strands whereas $α$-helices appear only when the temperature is lower than a certain threshold value. It is found that there exists an optimal temperature at which the correct secondary structures are predicted most accurately. We find that this temperature is close to the peak temperature of the specific heat. Changing the interaction window or carrying out longer simulations approaching equilibrium lead to little change in the optimal success rate. Our findings are in accord with the observation by Srinivasan and Rose that the secondary structures are mainly determined by local interactions and they appear in the early stage of folding.

cond-mat.stat-mech↗

arXiv2002

Folding Pathways of Prion and Doppel

The relevance of various residue positions for the stability and the folding characteristics of the prion protein are investigated by using molecular dynamics simulations of models exploiting the topology of the native state. Highly significant correlations are found between the most relevant sites in our analysis and the single point mutations known to be associated with the arousal of the genetic forms of prion disease (caused by the conformational change from the cellular to the scrapie isoform). Considerable insight into the conformational change is provided by comparing the folding process of prion and doppel (a newly discovered protein) sharing very similar native state topology: the folding pathways of the former can be grouped in two main classes according to which tertiary structure contacts are formed first enroute to the native state. For the latter a single class of pathways leads to the native state. Our results are consistent and supportive of the recent experimental findings that doppel lacks the scrapie isoform and that such remarkably different behavior results from differences in the region containing the two $β-$strands and the intervening helix.

cond-mat.stat-mech↗

arXiv2001

Protein threading by learning

Using techniques borrowed from statistical physics and neural networks, we determine the parameters, associated with a scoring function, that are chosen optimally to ensure complete success in threading tests in a training set of proteins. These parameters provide a quantitative measure of the propensities of amino acids to be buried or exposed and to be in a given secondary structure and are a good starting point for solving both the threading and design problems.

cond-mat.soft↗

arXiv2001

Mechanical denaturation of DNA: existence of a low temperature denaturation

Recent theoretical predictions on DNA mechanical separation induced by pulling forces are numerically tested within a model in which self-avoidance for DNA strands is fully taken into account. DNA strands are described by interacting pairs of self avoiding walks (SAW) which are pulled apart by a force applied at the two extremities. The whole phase diagram is spanned by extensive Monte Carlo (MC) simulations and the existence of a low temperature denaturation is confirmed. The basic features of the phase diagram and the re-entrant phase boundary are also obtained with a simple heuristic argument based on an energy-entropy estimate.

cond-mat.stat-mech↗

arXiv2001

Master Equation Approach to Molecular Motors

A master equation approach to molecular motors allows to describe a mechano-chemical cyclic system where chemical and translational degrees of freedom are treated on an equal footing. A generalized detailed balance condition in the out of equilibrium regime is shown to be compatible with the Fokker-Planck equation in the continuum limit. The Onsager reciprocity relations hold for stationary states close to equilibrium, provided the generalized detailed balance condition is satisfied. Semi-phenomenological considerations in the case of motor proteins lead to a discrete kinetics model, for which interesting observable quantities can be directly calculated and compared with experimental data.

cond-mat.stat-mech↗

arXiv2001

Conformations of Proteins in Equilibrium

We introduce a simple theoretical approach for an equilibrium study of proteins with known native state structures. We test our approach with results on well-studied globular proteins, Chymotrypsin Inhibitor (2ci2), Barnase and the alpha spectrin SH3 domain and present evidence for a hierarchical onset of order on lowering the temperature with significant organization at the local level even at high temperatures. A further application to the folding process of HIV-1 protease shows that the model can be reliably used to identify key folding sites that are responsible for the development of drug resistance .

cond-mat.stat-mech↗

arXiv2001

Geometrical aspects of protein folding

These lectures will address two questions. Is there a simple variational principle underlying the existence of secondary motifs in the native state of proteins? Is there a general approach which can qualitatively capture the salient features of the folding process and which may be useful for interpreting and guiding experiments? Here, we present three different approaches to the first question, which demonstrate the key role played by the topology of the native state of proteins. The second question pertaining to the folding dynamics of proteins remains a challenging problem -- a detailed description capturing the interactions between amino acids among each other and with the solvent is a daunting task. We address this issue building on the lessons learned in tackling the first question and apply the resulting method to the folding of various proteins including HIV protease and membrane proteins. The results that will be presented open a fascinating perspective: the two questions appear to be intimately related. The variety of results reported here all provide evidence in favour of the special criteria adopted by nature in the selection of viable protein folds, ranging from optimal compactness to maximum dynamical and geometrical accessibility of the native states.

cond-mat.stat-mech↗

arXiv2001

Dynamic modeling of gene expression data

We describe the time evolution of gene expression levels by using a time translational matrix to predict future expression levels of genes based on their expression levels at some initial time. We deduce the time translational matrix for previously published DNA microarray gene expression data sets by modeling them within a linear framework using the characteristic modes obtained by singular value decomposition. The resulting time translation matrix provides a measure of the relationships among the modes and governs their time evolution. We show that a truncated matrix linking just a few modes is a good approximation of the full time translation matrix. This finding suggests that the number of essential connections among the genes is small.

cond-mat.stat-mech↗

arXiv2001

Molecular Dynamics Studies on HIV-1 Protease: Drug Resistance and Folding Pathways

Drug resistance to HIV-1 Protease involves accumulation of multiple mutations in the protein. Here we investigate the role of these mutations by using molecular dynamics simulations which exploit the influence of the native-state topology in the folding process. Our calculations show that sites contributing to phenotypic resistance of FDA-approved drugs are among the most sensitive positions for the stability of partially folded states and should play a relevant role in the folding process. Furthermore, associations between amino acid sites mutating under drug treatment are shown to be statistically correlated. The striking correlation between clinical data and our calculations suggest a novel approach to the design of drugs tailored to bind regions crucial not only for protein function but also for folding.

cond-mat.stat-mech↗

arXiv2000

Learning effective amino acid interactions through iterative stochastic techniques

The prediction of the three-dimensional structures of the native state of proteins from the sequences of their amino acids is one of the most important challenges in molecular biology. An essential ingredient to solve this problem within coarse-grained models is the task of deducing effective interaction potentials between the amino acids. Over the years several techniques have been developed to extract potentials that are able to discriminate satisfactorily between the native and non-native folds of a pre-assigned protein sequence. In general, when these potentials are used in actual dynamical folding simulations, they lead to a drift of the native structure outside the quasi-native basin. In this study, we present and validate an approach to overcome this difficulty. By exploiting several numerical and analytical tools we set up a rigorous iterative scheme to extract potentials satisfying a pre-requisite of any viable potential: the stabilization of proteins within their native basin (less than 3-4 Å$ $ cRMS). The scheme is flexible and is demonstrated to be applicable to a variety of parametrizations of the energy function and provides, in each case, the optimal potentials.

cond-mat.stat-mech↗

arXiv2000

Force Dependence of the Michaelis Constant in a Two-State Ratchet Model for Molecular Motors

We present a quantitative analysis of recent data on the kinetics of ATP hydrolysis, which has presented a puzzle regarding the load dependence of the Michaelis constant. Within the framework of coarse grained two-state ratchet models, our analysis not only explains the puzzling data, but provides a modified Michaelis law, which could be useful as a guide for future experiments.

cond-mat.stat-mech↗

arXiv2000

Recurrent oligomers in proteins - an optimal scheme reconciling accurate and concise backbone representations in automated folding and design studies

A novel scheme is introduced to capture the spatial correlations of consecutive amino acids in naturally occurring proteins. This knowledge-based strategy is able to carry out optimally automated subdivisions of protein fragments into classes of similarity. The goal is to provide the minimal set of protein oligomers (termed ``oligons'' for brevity) that is able to represent any other fragment. At variance with previous studies where recurrent local motifs were classified, our concern is to provide simplified protein representations that have been optimised for use in automated folding and/or design attempts. In such contexts it is paramount to limit the number of degrees of freedom per amino acid without incurring in loss of accuracy of structural representations. The suggested method finds, by construction, the optimal compromise between these needs. Several possible oligon lengths are considered. It is shown that meaningful classifications cannot be done for lengths greater than 6 or smaller than 4. Different contexts are considered were oligons of length 5 or 6 are recommendable. With only a few dozen of oligons of such length, virtually any protein can be reproduced within typical experimental uncertainties. Structural data for the oligons is made publicly available.

cond-mat.soft↗