Highly Designable Protein Structures and Inter Monomer Interactions

By exact computer enumeration and combinatorial methods, we have calculated the designability of proteins in a simple lattice H-P model for the protein folding problem. We show that if the strength of the non-additive part of the interaction potential becomes larger than a critical value, the degree of designability of structures will depend on the parameters of potential. We also show that the existence of a unique ground state is highly sensitive to mutation in certain sites.Comment: 14 pages, Latex file, 3 latex and 6 eps figures are include

Viscosity Dependence of the Folding Rates of Proteins

The viscosity dependence of the folding rates for four sequences (the native state of three sequences is a beta-sheet, while the fourth forms an alpha-helix) is calculated for off-lattice models of proteins. Assuming that the dynamics is given by the Langevin equation we show that the folding rates increase linearly at low viscosities \eta, decrease as 1/\eta at large \eta and have a maximum at intermediate values. The Kramers theory of barrier crossing provides a quantitative fit of the numerical results. By mapping the simulation results to real proteins we estimate that for optimized sequences the time scale for forming a four turn \alpha-helix topology is about 500 nanoseconds, whereas the time scale for forming a beta-sheet topology is about 10 microseconds.Comment: 14 pages, Latex, 3 figures. One figure is also available at http://www.glue.umd.edu/~klimov/seq_I_H.html, to be published in Physical Review Letter

Glassy Dynamics of Protein Folding

A coarse grained model of a random polypeptide chain, with only discrete torsional degrees of freedom and Hookean springs connecting pairs of hydrophobic residues is shown to display stretched exponential relaxation under Metropolis dynamics at low temperatures with the exponent $\beta\simeq 1/4$, in agreement with the best experimental results. The time dependent correlation functions for fluctuations about the native state, computed in the Gaussian approximation for real proteins, have also been found to have the same functional form. Our results indicate that the energy landscape exhibits universal features over a very large range of energies and is relatively independent of the specific dynamics.Comment: RevTeX, 4 pages, multicolumn, including 5 figures; larger computations performed, error bars improve

Theta-point universality of polyampholytes with screened interactions

By an efficient algorithm we evaluate exactly the disorder-averaged statistics of globally neutral self-avoiding chains with quenched random charge $q_i=\pm 1$ in monomer i and nearest neighbor interactions $\propto q_i q_j$ on square (22 monomers) and cubic (16 monomers) lattices. At the theta transition in 2D, radius of gyration, entropic and crossover exponents are well compatible with the universality class of the corresponding transition of homopolymers. Further strong indication of such class comes from direct comparison with the corresponding annealed problem. In 3D classical exponents are recovered. The percentage of charge sequences leading to folding in a unique ground state approaches zero exponentially with the chain length.Comment: 15 REVTEX pages. 4 eps-figures . 1 tabl

Conformational Entropy of Compact Polymers

Exact results for the scaling properties of compact polymers on the square lattice are obtained from an effective field theory. The entropic exponent \gamma=117/112 is calculated, and a line of fixed points associated with interacting chains is identified; along this line \gamma varies continuously. Theoretical results are checked against detailed numerical transfer matrix calculations, which also yield a precise estimate for the connective constant \kappa=1.47280(1).Comment: 4 pages, 1 figur

A Solvable Model of Secondary Structure Formation in Random Hetero-Polymers

We propose and solve a simple model describing secondary structure formation in random hetero-polymers. It describes monomers with a combination of one-dimensional short-range interactions (representing steric forces and hydrogen bonds) and infinite range interactions (representing polarity forces). We solve our model using a combination of mean field and random field techniques, leading to phase diagrams exhibiting second-order transitions between folded, partially folded and unfolded states, including regions where folding depends on initial conditions. Our theoretical results, which are in excellent agreement with numerical simulations, lead to an appealing physical picture of the folding process: the polarity forces drive the transition to a collapsed state, the steric forces introduce monomer specificity, and the hydrogen bonds stabilise the conformation by damping the frustration-induced multiplicity of states.Comment: 24 pages, 14 figure

Freezing Transition of Random Heteropolymers Consisting of an Arbitrary Set of Monomers

Mean field replica theory is employed to analyze the freezing transition of random heteropolymers comprised of an arbitrary number ($q$) of types of monomers. Our formalism assumes that interactions are short range and heterogeneity comes only from pairwise interactions, which are defined by an arbitrary $q \times q$ matrix. We show that, in general, there exists a freezing transition from a random globule, in which the thermodynamic equilibrium is comprised of an essentially infinite number polymer conformations, to a frozen globule, in which equilibrium ensemble is dominated by one or very few conformations. We also examine some special cases of interaction matrices to analyze the relationship between the freezing transition and the nature of interactions involved.Comment: 30 pages, 1 postscript figur

Exploring the Levinthal limit in protein folding

According to the thermodynamic hypothesis, the native state of proteins is uniquely defined by their amino acid sequence. On the other hand, according to Levinthal, the native state is just a local minimum of the free energy and a given amino acid sequence, in the same thermodynamic conditions, can assume many, very different structures that are as thermodynamically stable as the native state. This is the Levinthal limit explored in this work. Using computer simulations, we compare the interactions that stabilize the native state of four different proteins with those that stabilize three non-native states of each protein and find that the nature of the interactions is very similar for all such 16 conformers. Furthermore, an enhancement of the degree of fluctuation of the non-native conformers can be explained by an insufficient relaxation to their local free energy minimum. These results favor Levinthal's hypothesis that protein folding is a kinetic non-equilibrium process.FCT - Foundation for Science and Technology, Portugal [UID/Multi/04326/2013]; Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP); Conselho Nacional de Desenvolvimento Cientia co e Tecnologico (CNPq

A New Monte Carlo Algorithm for Protein Folding

We demonstrate that the recently proposed pruned-enriched Rosenbluth method (P. Grassberger, Phys. Rev. E 56 (1997) 3682) leads to extremely efficient algorithms for the folding of simple model proteins. We test them on several models for lattice heteropolymers, and compare to published Monte Carlo studies. In all cases our algorithms are faster than all previous ones, and in several cases we find new minimal energy states. In addition to ground states, our algorithms give estimates for the partition sum at finite temperatures.Comment: 4 pages, Latex incl. 3 eps-figs., submitted to Phys. Rev. Lett., revised version with changes in the tex

DON content in oat grains in Norway related to weather conditions at different growth stages

High concentrations of the mycotoxin deoxynivalenol (DON), produced by Fusarium graminearum have occurred frequently in Norwegian oats recently. Early prediction of DON levels is important for farmers, authorities and the Cereal Industry. In this study, the main weather factors influencing myco-toxin accumulation were identified and two models to predict the risk of DON in oat grains in Norway were developed: (1) as a warning system for farmers to decide if and when to treat with fungicide, and (2) for authorities and industry to use at harvest to identify potential food safety problems. Oat grain samples from farmers’ fields were collected together with weather data (2004–2013) A mathematical model was developed and used to esti- mate phenology windows of growth stages in oats (til- lering, flowering etc.). Weather summarisations were then calculated within these windows, and the Spearman rank correlation factor calculated between DON- contamination in oats at harvest and the weather summarisations for each phenological window. DON contamination was most clearly associated with the weather conditions around flowering and close to har- vest. Warm, rainy and humid weather during and around flowering increased the risk of DON accumulation in oats, as did dry periods during germination/seedling growth and tillering. Prior to harvest, warm and humid weather conditions followed by cool and dry conditions were associated with a decreased risk of DON accumu- lation. A prediction model, including only pre-flowering weather conditions, adequately forecasted risk of DON contamination in oat, and can aid in decisions about fungicide treatments