Biomedical subjects

Ronen Zangi

Publications and source records attributed to Ronen Zangi.

9 recordsLinked to original sources

PubMed2006

Aggregation and dispersion of small hydrophobic particles in aqueous electrolyte solutions.

The effect of salts on the solvent-induced interactions between hydrophobic particles dispersed in explicit aqueous solution is investigated as a function of the salt's ionic charge density by molecular dynamics simulations. We demonstrate that aggregates of the hydrophobic particles can be formed or dissolved in response to changes in the charge density of the ions. Ions with high charge density increase the propensity of the hydrophobic particles to aggregate. This corresponds to stronger hydrophobic interactions and a decrease in the solubility (salting-out) of the hydrophobic particles. Ions with low charge density can either increase or decrease the propensity for aggregation depending on whether the concentration of the salt is low or high, respectively. At low concentrations of low charge density ions, the aggregate forms a "micelle-like" structure in which the ions are preferentially adsorbed at the surface of the aggregate. These "micelle-like" structures can be soluble in water so that the electrolyte can both increase the solubility and increase aggregation at the same time. We also find, that at the concentration of the hydrophobic particles studied (approximately 0.75 m), the aggregation process resembles a first-order transition in finite systems.

Absorption↗

PubMed2005

Physisorption of hydroxide ions from aqueous solution to a hydrophobic surface.

We present results from detailed molecular dynamics simulations revealing a counterintuitive spontaneous physical adsorption of hydroxide ions at a water/hydrophobic interface. The driving force for the migration of the hydroxide ions from the aqueous phase is the preferential orientation of the water molecules in the first two water layers away from the hydrophobic surface. This ordering of the water molecules generates an electrical potential gradient that strongly and favorably interacts with the dipole moment of the hydroxide ion. These findings offer a physical mechanism that explains intriguing experimental reports indicating that the interface between water and a nonionic surface is negatively charged.

Journal Article↗

PubMed2005

Characterization of the stereochemical selectivity of beta-hairpin formation by molecular dynamics simulations.

The stability of secondary structure motifs found in proteins is influenced by the choice of the configuration of the chiral centers present in the amino acid residues (i.e., D vs L). Experimental studies showed that the structural properties of the tetrapeptide (L)V(L)P(L)A(L)L (all-L) are drastically altered upon mutating the L-proline and the L-alanine by their d-enantiomers [J. Am. Chem. Soc. 1996, 118, 6975]. The all-L diastereomer is unstructured, experiencing little or no beta-hairpin formation, while the (L)V(D)P(D)A(L)L peptide exhibits a substantial population of beta-hairpin conformation. In this study, we perform molecular dynamics simulations to investigate the folding propensity of these two model peptides. The results confirm the experimental findings, namely, that the presence of d-amino acids in the loop region strongly induces beta-hairpin formation (a population increase from about 1.5% to 50% is observed). The major factor determining the different behavior is found to be the large difference in energy between the two diastereomers, approximately 22 kJ/mol, when they adopt a beta-hairpin structure. The higher energy observed for the all-L peptide is a consequence of none-ideal hydrogen bond formation and of steric repulsions. The results suggest that selective incorporation of D-amino acids in proteins can be used to enhance certain secondary structure elements. The kinetic behavior of the folding process observed in the simulations is also investigated. We find that the decay rate of the folded structure fits to a biexponential function, suggesting that the folding/unfolding process of a beta-hairpin is governed by two different mechanisms.

Amino Acid Substitution↗

PubMed2004

Electrofreezing of confined water.

We report results from molecular dynamics simulations of the freezing transition of TIP5P water molecules confined between two parallel plates under the influence of a homogeneous external electric field, with magnitude of 5 V/nm, along the lateral direction. For water confined to a thickness of a trilayer we find two different phases of ice at a temperature of T=280 K. The transformation between the two, proton-ordered, ice phases is found to be a strong first-order transition. The low-density ice phase is built from hexagonal rings parallel to the confining walls and corresponds to the structure of cubic ice. The high-density ice phase has an in-plane rhombic symmetry of the oxygen atoms and larger distortion of hydrogen bond angles. The short-range order of the two ice phases is the same as the local structure of the two bilayer phases of liquid water found recently in the absence of an electric field [J. Chem. Phys. 119, 1694 (2003)]. These high- and low-density phases of water differ in local ordering at the level of the second shell of nearest neighbors. The results reported in this paper, show a close similarity between the local structure of the liquid phase and the short-range order of the corresponding solid phase. This similarity might be enhanced in water due to the deep attractive well characterizing hydrogen bond interactions. We also investigate the low-density ice phase confined to a thickness of 4, 5, and 8 molecular layers under the influence of an electric field at T=300 K. In general, we find that the degree of ordering decreases as the distance between the two confining walls increases.

Journal Article↗

PubMed2004

Cooperative dynamics in two dimensions.

We report results from molecular dynamics simulations of cooperative motion in a quasi-two-dimensional system of colloid particles. We find that the onset of the deviation of the single-particle displacement distribution from Gaussian form starts in the liquid phase and extends, with increasing magnitude, through the hexatic phase into the crystalline phase. The time for which the deviation is maximum increases exponentially with the density. As the density increases toward the hexatic phase a third dynamical relaxation mode emerges. We argue that the collective motion is generated by superpositions of instantaneous normal mode vibrations, with lifetimes that increase with the density, along paths with strong bond-orientation correlation.

Journal Article↗

PubMed2003

Freezing transition and correlated motion in a quasi-two-dimensional colloid suspension.

Recent experiments have demonstrated that the deviation of the single-particle displacement distribution from Gaussian form in a dense quasi-two-dimensional colloid suspension is a result of heterogenous dynamics that involves cooperative motions of neighboring colloid particles [J. Chem. Phys. 47, 9142 (2001)]. In this paper, we report the results of molecular dynamics (MD) simulations of a quasi-two-dimensional assembly of nearly hard-sphere colloid particles. The colloid-colloid interaction we use is short ranged and everywhere repulsive; it is related to the Marcus-Rice (MR) and modified MR interactions used in a previous study [Phys. Rev. E 58, 7529 (1998)]. As is the case for those systems, the one we study supports liquid, hexatic, and solid phases. Our calculations show that the deviation of the single-particle displacement distribution from Gaussian form is present in the liquid phase, and that a sharp increase in its magnitude occurs at the liquidus density and extends into the crystalline phase. For densities greater than the liquidus density we find three dynamical relaxation processes that include, at intermediate times, a slowing down in the rate of growth of the diffusive displacement of a particle due to the cage effect. As the density increases toward the solidus density, the dependence of the mean squared displacement on time, at intermediate times, changes from sublinear to zero. The onset of the long-time relaxation mode corresponds to the time at which the deviation of the particle displacement distribution from Gaussian form is a maximum. At this time, which increases exponentially with the density, the self-part of the van Hove function exhibits multiple maxima with respect to r while the distinct part of the van Hove function is a maximum at the origin, thereby signaling jump dynamics. At long times the particle mean square displacement has diffusive character at all densities including solid phase densities. A remarkable feature of our findings is the continuity of character of the particle displacement from the liquid phase through the hexatic phase and into the solid phase. Cooperative jumps that lead to diffusive process in crystals can be explained by a mechanism that involves many such correlated hops in random locations and random directions (but along the crystallographic axes) thereby generating effective random walk behavior. We argue that the collective motion we have found is generated by superpositions of instantaneous normal mode vibrations along diffusive paths. The diffusive paths are along the directions with strong bond orientation correlation, and start to grow in amplitude rapidly on entry into the hexatic phase.

Biophysical Phenomena↗

PubMed2003

Monolayer ice.

We report results from molecular dynamics simulations of water under confinement and at ambient conditions that predict a first-order freezing transition from a monolayer of liquid water to a monolayer of ice induced by increasing the distance between the confining parallel plates. Since a slab geometry is incompatible with a tetrahedral arrangement of the sp(3) hybridized oxygen of water, the freezing is coupled to a linear buckling transition. By exploiting the ordered out-of-plane displacement of the molecules in the buckled phase the distortion of the hydrogen bonds is minimized.

Journal Article↗

PubMed2003

Sampling and convergence in free energy calculations of protein-ligand interactions: the binding of triphenoxypyridine derivatives to factor Xa and trypsin.

The binding of a set of 10 triphenoxypyridine derivatives to two serine proteases, factor Xa and trypsin, has been used to analyze factors related to sampling and convergence in free energy calculations based on molecular dynamics simulation techniques. The inhibitors investigated were initially proposed as part of the Critical Assessment of Techniques for Free Energy Evaluation (CATFEE) project for which no experimental results nor any assessment of the predictions submitted by various groups have ever been published. The inhibitors studied represent a severe challenge for explicit free energy calculations. The mutations from one compound to another involve up to 19 atoms, the creation and annihilation of net charge and several alternate binding modes. Nevertheless, we demonstrate that it is possible to obtain highly converged results (+/- 5-10 kJ/mol) even for such complex multi-atom mutations by simulating on a nanosecond time scale. This is achieved by using soft-core potentials to facilitate the creation and deletion of atoms and by a careful choice of mutation pathway. The results show that given modest computational resources, explicit free energy calculations can be successfully applied to realistic problems in drug design.

Binding Sites↗

PubMed2002

Molecular dynamics study of the folding of hydrophobin SC3 at a hydrophilic/hydrophobic interface.

Hydrophobins are fungal proteins that self-assemble at hydrophilic/hydrophobic interfaces into amphipathic membranes. These assemblages are extremely stable and posses the remarkable ability to invert the polarity of the surface on which they are adsorbed. Neither the three-dimensional structure of a hydrophobin nor the mechanism by which they function is known. Nevertheless, there are experimental indications that the self-assembled form of the hydrophobins SC3 and EAS at a water/air interface is rich with beta-sheet secondary structure. In this paper we report results from molecular dynamics simulations, showing that fully extended SC3 undergoes fast (approximately 100 ns) folding at a water/hexane interface to an elongated planar structure with extensive beta-sheet secondary elements. Simulations in each of the bulk solvents result in a mainly unstructured globular protein. The dramatic enhancement in secondary structure, whether kinetic or thermodynamic in origin, highlights the role interfaces between phases with large differences in polarity can have on folding. The partitioning of the residue side-chains to one of the two phases can serve as a strong driving force to initiate secondary structure formation. The interactions of the side-chains with the environment at an interface can also stabilize configurations that otherwise would not occur in a homogenous solution.

Algorithms↗