arXiv subjects

Kim Sneppen

Publications and source records attributed to Kim Sneppen.

At least 73 records · Page 4Linked to original sources

arXiv2003

Sensitivity of Phage Lambda upon Variations of the Gibbs Free Energy

We investigate the sensitivity of production rates (activities) of the regulatory proteins CI (repressor) and Cro at the right operator (O_R}) of bacteriophage lambda. The DNA binding energies of CI, Cro, and RNA polymerase are perturbed to check the uncertainty of the activity, due to the experimental error, by means of a computational scattering method according to which the binding energies are simultaneously chosen at random around the literature values, with a width corresponding to the experimental error. In a grand canonical ensemble, with the randomly drawn protein-DNA binding energies as input, we calculate the corresponding activities of the promoters P_RM and P_R. By repeating this procedure we obtain a mean value of the activity that roughly corresponds to wild-type (unperturbed) activity. The standard deviation emerging from this scheme, a measure of the sensitivity due to experimental error, is significant (typically > 20% relative to wild-type activity), but still the promoter activities are sufficiently separated to make the switch feasible. We also suggest a new compact way of presenting repressor and Cro data.

cond-mat.stat-mech↗

arXiv2003

Upstream Plasticity and Downstream Robustness in Evolution of Molecular Networks

Evolving biomolecular networks have to combine the stability against perturbations with flexibility allowing their constituents to assume new roles in the cell. Gene duplication followed by functional divergence of associated proteins is a major force shaping molecular networks in living organisms. Recent availability of system-wide data for yeast S. Cerevisiae allow us to access the effects of gene duplication on robustness and plasticity of molecular networks. We demonstrate that the upstream transcriptional regulation of duplicated genes diverges fast, losing on average 4% of their common transcription factors for every 1% divergence of their amino acid sequences. In contrast, the set of physical interaction partners of their protein products changes much slower. The relative stability of downstream functions of duplicated genes, is further corroborated by their ability to substitute for each other in gene knockout experiments. We believe that the combination of the upstream plasticity and the downstream robustness is a general feature determining the evolvability of molecular networks.

q-bio.MN↗

arXiv2003

Modeling Dynamics of Information Networks

We propose an information-based model for network dynamics in which imperfect information leads to networks where the different vertices have widely different number of edges to other vertices, and where the topology has hierarchical features. The possibility to observe scale free networks is linked to a minimally connected system where hubs remain dynamic.

cond-mat.dis-nn↗

arXiv2003

Localization of Denaturation Bubbles in Random DNA Sequences

We study the thermodynamic and dynamic behaviors of twist-induced denaturation bubbles in a long, stretched random sequence of DNA. The small bubbles associated with weak twist are delocalized. Above a threshold torque, the bubbles of several tens of bases or larger become preferentially localized to \AT-rich segments. In the localized regime, the bubbles exhibit ``aging'' and move around sub-diffusively with continuously varying dynamic exponents. These properties are derived using results of large-deviation theory together with scaling arguments, and are verified by Monte-Carlo simulations.

cond-mat.stat-mech↗

arXiv2002

Modularity and Extreme Edges of the Internet

We study the spectral properties of a diffusion process taking place on the Internet network focusing on the slowest decaying modes. These modes allow us to identify an underlying modular structure of the Internet roughly corresponding to individual countries. For instance in the slowest decaying mode the diffusion current flows from Russia towards US military sites. These two regions thus constitute the extreme edges of the Internet. Quantitatively the modular structure of the Internet manifests itself in approximately 10 times larger participation ratio of its slow decaying modes compared to the null model - a random scale-free network. We propose to use the fraction of nodes participating in slow decaying modes as a general measure of the modularity of a network. For the 100 slowest decaying modes of the Internet we measured this fraction to be around 30%. Finally we suggest, that the degree of isolation of an individual module can be assessed by comparing its participation in different diffusion modes. Using the proportionality of response as a criterion we find that the independent module approximation works well for the Internet.

cond-mat.stat-mech↗

arXiv2002

Pattern Detection in Complex Networks: Correlation Profile of the Internet

A general scheme for detecting and analyzing topological patterns in large complex networks is presented. In this scheme the network in question is compared with its properly randomized version that preserves some of its low-level topological properties. Statistically significant deviation of any measurable property of a network from this null model likely reflect its design principles and/or evolutionary history. We illustrate this basic scheme on the example of the correlation profile of the Internet quantifying correlations between connectivities of its neighboring nodes. This profile distinguishes the Internet from previously studied molecular networks with a similar scale-free connectivity distribution. We finally demonstrate that clustering in a network is very sensitive to both the connectivity distribution and its correlation profile and compare the clustering in the Internet to the appropriate null model.

cond-mat.stat-mech↗

arXiv2002

Specificity and stability in topology of protein networks

Molecular networks guide the biochemistry of a living cell on multiple levels: its metabolic and signalling pathways are shaped by the network of interacting proteins, whose production, in turn, is controlled by the genetic regulatory network. To address topological properties of these two networks we quantify correlations between connectivities of interacting nodes and compare them to a null model of a network, in which al links were randomly rewired. We find that for both interaction and regulatory networks, links between highly connected proteins are systematically suppressed, while those between a highly-connected and low-connected pairs of proteins are favored. This effect decreases the likelihood of cross talk between different functional modules of the cell, and increases the overall robustness of a network by localizing effects of deleterious perturbations.

cond-mat.soft↗

arXiv2001

Profit Profiles in Correlated Markets

We consider a financial market where the asset price follows a fractional Brownian motion. We introduce a family of investment strategies, and quantify profit possibilities for both persistent and antipersistant markets.

cond-mat.stat-mech↗

arXiv2000

Stability Puzzles in Phage Lambda

The lysogeny maintenance switch in phage lambda is one of the simplest examples on the molecular level of computation, command and control in a living system. If, following infection of the bacterium E. coli, the virus enters the lysogenic pathway, it represses its developmental functions, and integrates its DNA into the host chromosome. In this state the prophage may be passively replicated for many generations of E. coli. In fact, this repressed state is intrinsically more stable than the gene encoding the repressor. We develop a mathematical formalism to predict the stability of such epigenetic states from affinities of the molecular components. We apply the model to the behavior of recently published mutants at the right operator complex of lambda, and find that the reported stability indicates that the current view of the switch is incomplete. The approach described here should be generally applicable to the stability of expressed states

cond-mat.soft↗

arXiv2000

A protein model exhibiting three folding transitions

We explain the physical basis of a model for small globular proteins with water interactions. The water is supposed to access the protein interior in an "all-or-none" manner during the unfolding of the protein chain. As a consequence of this mechanism (somewhat speculative), the model exhibits fundamental aspects of protein thermodynamics, as cold, and warm unfolding of the polypeptide chain, and hence decreasing the temperature below the cold unfolding the protein folds again, accordingly the heat capacity has three characteristic peaks. The cold and warm unfolding has a sharpness close to a two-state system, while the cold folding is a transition where the intermediate states in the folding is energetical close to the folded/unfolded states, yielding a less sharp transition. The entropy of the protein chain causes both the cold folding and the warm unfolding.

cond-mat↗

arXiv2000

Thermodynamical implications of a protein model with water interactions

We refine a protein model that reproduces fundamental aspects of protein thermodynamics. The model exhibits two transitions, hot and cold unfolding. The number of relevant parameters is reduced to three: 1) binding energy of folding relative to the orientational energy of bound water, 2) ratio of degrees of freedom between the folded and unfolded protein chain and 3) the number of water molecules that can access the hydrophobic parts of the protein interior. By increasing the number of water molecules in the model, the separation between the two peaks in the heat capacity curve decreases, which is more consistent with experimental data. We also show that if we, as a speculative assumption, assign effectively only two distinct energy levels for the bound water molecules, the hot peak in the heat capacity curve will be larger than the cold peak, in accordance with experimental observations.

cond-mat↗

arXiv2000

Parametrization of Multiple Pathways in Proteins: Fast Folding versus Tight Transitions

Growing experimental evidence shows that proteins follow one or a few distinct paths when folding. We propose in this paper a procedure to parametrize these observed pathways, and from this parametrization construct effective Hamiltonians for the proteins. We furthermore study the denaturated-native transitions for a wide class of possible effective Hamiltonians based on this scheme, and find that the sharpness (tightness) of the transitions typically are close to their theoretical maximum and thus in quantitative accordance with the sharp folding transition observed for single domain proteins. Finally we demonstrate that realistic folding times are typical for the proposed class of Hamiltonians, and we discuss the implication of the predicted entropy barriers on the temperature dependence of the folding times.

cond-mat↗

arXiv2000

Physics of Fashion Fluctuations

We consider a market where many agents trade many different types of products with each other. We model development of collective modes in this market, and quantify these by fluctuations that scale with time with a Hurst exponent of about 0.7. We demonstrate that individual products in the model occationally become globally accepted means of exchange, and simultaneously become very actively traded. Thus collective features similar to money spontaneously emerge, without any a priori reason.

cond-mat↗

arXiv2000

Robustness as an Evolutionary Principle

We suggest to simulate evolution of complex organisms constrained by the sole requirement of robustness in their expression patterns. This scenario is illustrated by evolving discrete logical networks with epigenetic properties. Evidence for dynamical features in the evolved networks is found that can be related to biological observables.

cond-mat.stat-mech↗

arXiv2000

Modelling an Imperfect Market

We propose a simple market model where agents trade different types of products with each other by using money, relying only on local information. Value fluctuations of single products, combined with the condition of maximum profit in transactions, readily lead to persistent fluctuations in the wealth of individual agents.

cond-mat↗

arXiv1999

Pathways in Two-State Protein Folding

The thermodynamics of proteins indicate that folding/unfolding takes place either through stable intermediates or through a two-state process without intermediates. The rather short folding times of the two-state process indicate that folding is guided. We reconcile these two seemingly contradictory observations quantitatively in a schematic model of protein folding. We propose a new dynamical transition temperature which is lower than the thermodynamic one, in qualitative agreement with in vivo measurement of protein stability using E.coli. Finally we demonstrate that our framework is easily generalized to encompass cold unfolding, and make predictions that relate the sharpness of the cold and hot unfolding transitions.

cond-mat↗

arXiv1999

Thermodynamics of Heat Shock Response

Production of heat shock proteins are induced when a living cell is exposed to a rise in temperature. The heat shock response of protein DnaK synthesis in E.coli for temperature shifts from temperature T to T plus 7 degrees, respectively to T minus 7 degrees is measured as function of the initial temperature T. We observe a reversed heat shock at low T. The magnitude of the shock increases when one increase the distance to the temperature $T_0 \approx 23^o$, thereby mimicking the non monotous stability of proteins at low temperature. Further we found that the variation of the heat shock with T quantitatively follows the thermodynamic stability of proteins with temperature. This suggest that stability related to hot as well as cold unfolding of proteins is directly implemented in the biological control of protein folding. We demonstrate that such an implementation is possible in a minimalistic chemical network.

cond-mat↗

arXiv1999

A Model for the Thermodynamics of Globular Proteins

Comments: 6 pages RevTeX, 6 Postscript figures. We review a statistical mechanics treatment of the stability of globular proteins based on a simple model Hamiltonian taking into account protein self interactions and protein-water interactions. The model contains both hot and cold folding transitions. In addition it predicts a critical point at a given temperature and chemical potential of the surrounding water. The universality class of this critical point is new.

cond-mat↗