Solvation vs. freezing in a heteropolymer globule

We address the response of a random heteropolymer to preferential solvation of certain monomer types at the globule-solvent interface. For each set of monomers that can comprise the molecule's surface, we represent the ensemble of allowed configurations by a Gaussian distribution of energy levels, whose mean and variance depend on the set's composition. Within such a random energy model, mean surface composition is proportional to solvation strength under most conditions. The breadth of this linear response regime arises from approximate statistical independence of surface and volume energies. For a diverse set of monomer types, the excess of solvophilic monomers at the surface is large only for very strong solvent preference, even in the ground state.Comment: 10 pages, 1 figur

Analytical description of finite size effects for RNA secondary structures

The ensemble of RNA secondary structures of uniform sequences is studied analytically. We calculate the partition function for very long sequences and discuss how the cross-over length, beyond which asymptotic scaling laws apply, depends on thermodynamic parameters. For realistic choices of parameters this length can be much longer than natural RNA molecules. This has to be taken into account when applying asymptotic theory to interpret experiments or numerical results.Comment: 10 pages, 13 figures, published in Phys. Rev.

Design of Copolymeric Materials

We devise a method for designing materials that will have some desired structural characteristics. We apply it to multiblock copolymers that have two different types of monomers, A and B. We show how to determine what sequence of A's and B's should be synthesised in order to give a particular structure and morphology. %For example in a melt of such %polymers, one may wish to engineer a body-centered %cubic structure. Using this method in conjunction with the theory of microphase separation developed by Leibler, we show it is possible to efficiently search for a desired morphology. The method is quite general and can be extended to design isolated heteropolymers, such as proteins, with desired structural characteristics. We show that by making certain approximations to the exact algorithm, a method recently proposed by Shakhnovich and Gutin is obtained. The problems with this method are discussed and we propose an improved approximate algorithm that is computationally efficient.Comment: 15 pages latex 2.09 and psfig, 1 postscript figure

Geometrically Reduced Number of Protein Ground State Candidates

Geometrical properties of protein ground states are studied using an algebraic approach. It is shown that independent from inter-monomer interactions, the collection of ground state candidates for any folded protein is unexpectedly small: For the case of a two-parameter Hydrophobic-Polar lattice model for $L$-mers, the number of these candidates grows only as $L^2$. Moreover, the space of the interaction parameters of the model breaks up into well-defined domains, each corresponding to one ground state candidate, which are separated by sharp boundaries. In addition, by exact enumeration, we show there are some sequences which have one absolute unique native state. These absolute ground states have perfect stability against change of inter-monomer interaction potential.Comment: 9 page, 4 ps figures are include

Updating ESA's Earth System Model for gravity mission simulation studies: 1. Model description and validation

The ability of any satellite gravity mission concept to monitor mass transport processes in the Earth system is typically tested well ahead of its implementation by means of various simulation studies. Those studies often extend from the simulation of realistic orbits and instrumental data all the way down to the retrieval of global gravity field solution time-series. Basic requirement for all these simulations are realistic representations of the spatio-temporal mass variability in the different sub-systems of the Earth, as a source model for the orbit computations. For such simulations, a suitable source model is required to represent (i) high-frequency (i.e., subdaily to weekly) mass variability in the atmosphere and oceans, in order to realistically include the effects of temporal aliasing due to non-tidal high-frequency mass variability into the retrieved gravity fields. In parallel, (ii) low-frequency (i.e., monthly to interannual) variability needs to be modelled with realistic amplitudes, particularly at small spatial scales, in order to assess to what extent a new mission concept might provide further insight into physical processes currently not observable. The new source model documented here attempts to fulfil both requirements: Based on ECMWF’s recent atmospheric reanalysis ERA-Interim and corresponding simulations from numerical models of the other Earth system components, it offers spherical harmonic coefficients of the time-variable global gravity field due to mass variability in atmosphere, oceans, the terrestrial hydrosphere including the ice-sheets and glaciers, as well as the solid Earth. Simulated features range from sub-daily to multiyear periods with a spatial resolution of spherical harmonics degree and order 180 over a period of 12 years. In addition to the source model, a de-aliasing model for atmospheric and oceanic high-frequency variability with augmented systematic and random noise is required for a realistic simulation of the gravity field retrieval process, whose necessary error characteristics are discussed. The documentation of the updated ESA Earth System Model (updated ESM) for gravity mission simulation studies is organized as follows: The characteristics of the updated ESM along with some basic validation is presented in Volume 1. A detailed comparison to the original ESA ESM (Gruber et al., 2011) is provided in Volume 2, while Volume 3 contains the description of a strategy to derive realistic errors for the de-aliasing model of high-frequency mass variability in atmosphere and ocean

Free Energy Self-Averaging in Protein-Sized Random Heteropolymers

Current theories of heteropolymers are inherently macrpscopic, but are applied to folding proteins which are only mesoscopic. In these theories, one computes the averaged free energy over sequences, always assuming that it is self-averaging -- a property well-established only if a system with quenched disorder is macroscopic. By enumerating the states and energies of compact 18, 27, and 36mers on a simplified lattice model with an ensemble of random sequences, we test the validity of the self-averaging approximation. We find that fluctuations in the free energy between sequences are weak, and that self-averaging is a valid approximation at the length scale of real proteins. These results validate certain sequence design methods which can exponentially speed up computational design and greatly simplify experimental realizations.Comment: 4 pages, 3 figure

Universal behavior of localization of residue fluctuations in globular proteins

Localization properties of residue fluctuations in globular proteins are studied theoretically by using the Gaussian network model. Participation ratio for each residue fluctuation mode is calculated. It is found that the relationship between participation ratio and frequency is similar for all globular proteins, indicating a universal behavior in spite of their different size, shape, and architecture.Comment: 4 pages, 3 figures. To appear in Phys. Rev.

An Approach to Web-Scale Named-Entity Disambiguation

We present a multi-pass clustering approach to large scale. wide-scope named-entity disambiguation (NED) oil collections of web pages. Our approach Uses name co-occurrence information to cluster and hence disambiguate entities. and is designed to handle NED on the entire web. We show that on web collections, NED becomes increasing), difficult as the corpus size increases, not only because of the challenge of scaling the NED algorithm, but also because new and surprising facets of entities become visible in the data. This effect limits the potential benefits for data-driven approaches of processing larger data-sets, and suggests that efficient clustering-based disambiguation methods for the web will require extracting more specialized information front documents

Prediction of Optimal Folding Routes of Proteins That Satisfy the Principle of Lowest Entropy Loss: Dynamic Contact Maps and Optimal Control

An optimization model is introduced in which proteins try to evade high energy regions of the folding landscape, and prefer low entropy loss routes during folding. We make use of the framework of optimal control whose convenient solution provides practical and useful insight into the sequence of events during folding. We assume that the native state is available. As the protein folds, it makes different set of contacts at different folding steps. The dynamic contact map is constructed from these contacts. The topology of the dynamic contact map changes during the course of folding and this information is utilized in the dynamic optimization model. The solution is obtained using the optimal control theory. We show that the optimal solution can be cast into the form of a Gaussian Network that governs the optimal folding dynamics. Simulation results on three examples (CI2, Sso7d and Villin) show that folding starts by the formation of local clusters. Non-local clusters generally require the formation of several local clusters. Non-local clusters form cooperatively and not sequentially. We also observe that the optimal controller prefers “zipping” or small loop closure steps during folding. The folding routes predicted by the proposed method bear strong resemblance to the results in the literature

Monte Carlo Procedure for Protein Design

A new method for sequence optimization in protein models is presented. The approach, which has inherited its basic philosophy from recent work by Deutsch and Kurosky [Phys. Rev. Lett. 76, 323 (1996)] by maximizing conditional probabilities rather than minimizing energy functions, is based upon a novel and very efficient multisequence Monte Carlo scheme. By construction, the method ensures that the designed sequences represent good folders thermodynamically. A bootstrap procedure for the sequence space search is devised making very large chains feasible. The algorithm is successfully explored on the two-dimensional HP model with chain lengths N=16, 18 and 32.Comment: 7 pages LaTeX, 4 Postscript figures; minor change