Unfolding designable structures

Among an infinite number of possible folds, nature has chosen only about 1000 distinct folds to form protein structures. Theoretical studies suggest that selected folds are intrinsically more designable than others; these selected folds are unusually stable, a property called the designability principle. In this paper we use the 2D hydrophobic-polar lattice model to classify structures according to their designability, and Langevin dynamics to account for their time evolution. We demonstrate that, among all possible folds, the more designable ones are easier to unfold due to their large number of surface-core bonds.Comment: 10 pages, 4 figures, Proceeding of the 3rd International Conference NEXT-SigmaPh

Microscopic mechanism for cold denaturation

We elucidate the mechanism of cold denaturation through constant-pressure simulations for a model of hydrophobic molecules in an explicit solvent. We find that the temperature dependence of the hydrophobic effect is the driving force/induces/facilitates cold denaturation. The physical mechanism underlying this phenomenon is identified as the destabilization of hydrophobic contact in favor of solvent separated configurations, the same mechanism seen in pressure induced denaturation. A phenomenological explanation proposed for the mechanism is suggested as being responsible for cold denaturation in real proteins

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Models of the stability of proteins

Although the native conformation of a protein is thermodynamically its most stable form, this stability is only marginal. As a consequence, globular proteins have a certain amount of flexibility in their backbones which allows for conformational changes in the course of their biological function. In the course of this thesis, we study protein models at the edge of stability in different contexts: (1) First, we use molecular dynamics to determine the force needed to rupture a chain molecule (an unfolded protein) being stretched at constant loading rate and temperature. When all energy bonds of the molecule are identical, we find that the force F depends on the pulling rate r and temperature T according to F ~ const -- T 1/3|ln(r/T)|1/3 When a single weak bond is introduced, this result is modified to F ~ const -- T2/3|ln(r/ T)|2/3 This scaling, which is model independent, can be used with force-spectroscopy experiment to quantitatively extract relevant microscopic parameters of biomolecules. (2) Second, we study the structural stability of models of proteins for which the selected folds are unusually stable to mutation, that is, designable. A two-dimensional hydrophobic-polar lattice model is used to determine designable folds and these folds were investigated under shear through Langevin dynamics. We find that the phase diagram of these proteins depends on their designability. In particular, highly designable folds are found to be weaker, i.e. easier to unfold, than low designable ones. This is argued to be related to protein flexibility. (3) Third, we study the mechanism of cold denaturation through constant-pressure simulations for a model of hydrophobic molecules in an explicit solvent. We find that the temperature dependence of the hydrophobic effect is the driving force for cold denaturation. The physical mechanism underlying this phenomenon is identified as the destabilization of hydrophobic contact in favor of solvent separated configurations, the same mechanism seen in pressure induced denaturation. A phenomenological explanation proposed for the mechanism is suggested as being responsible for cold denaturation in real proteins

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Cutting Ice: Nanowire Regelation

Even below its normal melting temperature, ice melts when subjected to high pressure and refreezes once the pressure is lifted. A classic demonstration of this regelation phenomenon is the passing of a thin wire through a block of ice when sufficient force is exerted. Here we present a molecular-dynamics study of a nanowire cutting through ice to unravel the molecular level mechanisms responsible for regelation. In particular, we show that the transition from a stationary to a moving wire due to increased driving force changes from symmetric and continuous to asymmetric and discontinuous as a hydrophilic wire is replaced by a hydrophobic one. This is explained at the molecular level in terms of the wetting properties of the wire.Peer reviewe

Antifungal nanofibers made by controlled release of sea animal derived peptide

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