A model for the accidental catalysis of protein unfolding in vivo

Activated processes such as protein unfolding are highly sensitive to heterogeneity in the environment. We study a highly simplified model of a protein in a random heterogeneous environment, a model of the in vivo environment. It is found that if the heterogeneity is sufficiently large the total rate of the process is essentially a random variable; this may be the cause of the species-to-species variability in the rate of prion protein conversion found by Deleault et al. [Nature, 425 (2003) 717].Comment: 5 pages, 2 figure

A refined hydrogen bond potential for flexible protein models

One of the major disadvantages of coarse-grained hydrogen bond potentials, for their use in protein folding simulations, is the appearance of abnormal structures when these potentials are used in flexible chain models, and no other geometrical restrictions or energetic contributions are defined into the system.We have efficiently overcome this problem, for chains of adequate size in a relevant temperature range, with a refined coarse-grained hydrogen bond potential. With it, we have been able to obtain nativelike alpha-helices and beta-sheets in peptidic systems, and successfully reproduced the competition between the populations of these secondary structure elements by the effect of temperature and concentration changes. In this manuscript we detail the design of the interaction potential and thoroughly examine its applicability in energetic and structural terms, considering factors such as chain length, concentration, and temperature

Response of the Brazilian gravitational wave detector to signals from a black hole ringdown

It is assumed that a black hole can be disturbed in such a way that a ringdown gravitational wave would be generated. This ringdown waveform is well understood and is modelled as an exponentially damped sinusoid. In this work we use this kind of waveform to study the performance of the SCHENBERG gravitational wave detector. This first realistic simulation will help us to develop strategies for the signal analysis of this Brazilian detector. We calculated the signal-to-noise ratio as a function of frequency for the simulated signals and obtained results that show that SCHENBERG is expected to be sensitive enough to detect this kind of signal up to a distance of $\sim 20\mathrm{kpc}$.Comment: 5 pages, 4 figures, Amaldi 5 Conference Proceedings contribution. Submitted to Class. Quantum Gra

Lattice model for cold and warm swelling of polymers in water

We define a lattice model for the interaction of a polymer with water. We solve the model in a suitable approximation. In the case of a non-polar homopolymer, for reasonable values of the parameters, the polymer is found in a non-compact conformation at low temperature; as the temperature grows, there is a sharp transition towards a compact state, then, at higher temperatures, the polymer swells again. This behaviour closely reminds that of proteins, that are unfolded at both low and high temperatures.Comment: REVTeX, 5 pages, 2 EPS figure

Finite size effects on thermal denaturation of globular proteins

Finite size effects on the cooperative thermal denaturation of proteins are considered. A dimensionless measure of cooperativity, Omega, scales as N^zeta, where N is the number of amino acids. Surprisingly, we find that zeta is universal with zeta = 1 + gamma, where the exponent gamma characterizes the divergence of the susceptibility for a self-avoiding walk. Our lattice model simulations and experimental data are consistent with the theory. Our finding rationalizes the marginal stability of proteins and substantiates the earlier predictions that the efficient folding of two-state proteins requires the folding transition temperature to be close to the collapse temperature.Comment: 3 figures. Physical Review Letters (in press

Discrete Breathers in a Realistic Coarse-Grained Model of Proteins

We report the results of molecular dynamics simulations of an off-lattice protein model featuring a physical force-field and amino-acid sequence. We show that localized modes of nonlinear origin (discrete breathers) emerge naturally as continuations of a subset of high-frequency normal modes residing at specific sites dictated by the native fold. In the case of the small $\beta$-barrel structure that we consider, localization occurs on the turns connecting the strands. At high energies, discrete breathers stabilize the structure by concentrating energy on few sites, while their collapse marks the onset of large-amplitude fluctuations of the protein. Furthermore, we show how breathers develop as energy-accumulating centres following perturbations even at distant locations, thus mediating efficient and irreversible energy transfers. Remarkably, due to the presence of angular potentials, the breather induces a local static distortion of the native fold. Altogether, the combination of this two nonlinear effects may provide a ready means for remotely controlling local conformational changes in proteins.Comment: Submitted to Physical Biolog

Sequence Dependence of Self-Interacting Random Chains

We study the thermodynamic behavior of the random chain model proposed by Iori, Marinari and Parisi, and how this depends on the actual sequence of interactions along the chain. The properties of randomly chosen sequences are compared to those of designed ones, obtained through a simulated annealing procedure in sequence space. We show that the transition to the folded phase takes place at a smaller strength of the quenched disorder for designed sequences. As a result, folding can be relatively fast for these sequences.Comment: 14 pages, uuencoded compressed postscript fil

Thermodynamics of protein folding: a random matrix formulation

The process of protein folding from an unfolded state to a biologically active, folded conformation is governed by many parameters e.g the sequence of amino acids, intermolecular interactions, the solvent, temperature and chaperon molecules. Our study, based on random matrix modeling of the interactions, shows however that the evolution of the statistical measures e.g Gibbs free energy, heat capacity, entropy is single parametric. The information can explain the selection of specific folding pathways from an infinite number of possible ways as well as other folding characteristics observed in computer simulation studies.Comment: 21 Pages, no figure