Biomedical subjects

S Melchionna

Publications and source records attributed to S Melchionna.

9 recordsLinked to original sources

PubMed2006

Molecular dynamics simulation of ratchet motion in an asymmetric nanochannel.

The persistence of ratchet effects, i.e., nonzero mass flux under a zero-mean time-dependent drive, when many-body interactions are present, is studied via molecular dynamics (MD) simulations of a simple liquid flowing in an asymmetric nanopore. The results show that (i) ratchet effects persist under many-body density correlations induced by the forcing; (ii) two distinct linear responses (flux proportional to the drive amplitude) appear under strong loads. One regime has the same conductivity of linear response theory up to a forcing of about 10 kT, while the second displays a smaller conductivity, the difference in responses is due to geometric effects alone. (iii) Langevin simulations based on a naive mapping of the many-body equilibrium bulk diffusivity, D, onto the damping rate, gamma are also found to yield two distinct linear responses. However, in both regimes, the flux is significantly smaller than the one of MD simulations.

Computer Simulation↗

PubMed2006

The role of water coordination in binary mixtures. A study of two model amphiphilic molecules in aqueous solutions by molecular dynamics and NMR.

Two binary aqueous mixtures which contain the small amphiphilic molecules TMAO (trimethylamine-N-oxide) and TBA (tert-butyl alcohol) have been investigated by molecular dynamics simulations and NMR chemical shift and self-diffusion measurements. TMAO is an osmolyte, while TBA is a monohydrate alcohol. Both possess bulky hydrophobic groups and polar heads, namely, NO in TMAO and OH in TBA. The hydrophilic/hydrophobic content of these isosteric molecules strongly modulates the structure and dynamics of the hydration shell, which is thought to be responsible for the effects observed on proteins and phospholipids. Simulation results, especially on hydrogen-bond networking, spatial correlations, and self-diffusivity, are consistent with NMR data and agree well with previous numerical studies on similar solutions. The methods employed allow the elucidation of the microscopic features of the solutions. For TBA solutions, the hydration shell is found to have a low density and a large spatial spread, and thus, above the molar fraction of 0.03, reduction of hydrophobic hydration drives self-aggregation of the solute. This effect does not take place in TMAO solutions, where the hydration shell is more compact and stable, maintaining its structure over a wider range of solute concentrations.

Computer Simulation↗

PubMed2001

Accurate calculation of three-body depletion interactions.

We compute three-body depletion interactions in a hard-sphere mixture within the framework of density-functional theory and by considering the infinite dilution limit of the functional. The results look very accurate and show three-body interactions much smaller than the pair depletion ones, revealing that these are strongly influenced by correlations and have a decay length similar to the two-body depletion potential. The results are compared with the predictions of the Asakura-Oosawa model for the triplet interactions.

Journal Article↗

PubMed2001

Molecular characterization of a laminin-derived oligopeptide with implications in biomimetic applications.

The molecular properties of the laminin-derived oligopeptide, H-CDPGYIGSR-NH2, have been investigated with the aid of a tandem computer simulation/experimental approach. The simulation studies placed a particular emphasis on studying the oligopeptide in aqueous media, as well as in a grafted or immobilized state. The simulations revealed the presence of a stable double hydrogen bond between arginine (R) and aspartic acid (D) residues. The mutation of the terminal arginine with lysine, another hydrophilic and positively charged amino acid, resulted in a drastic structural change, thus suggesting a major role of the terminal arginine residue in the overall oligopeptide's conformation and, hence, its bioactivity. In addition, the involvement of the aspartic acid residue in overall peptide structural stabilization also illustrates a previously undetermined role for this region (i.e. CDPG) of the oligopeptide. A subsequent in vitro experiment demonstrated a significant loss of bioactivity upon mutating the terminal residue from arginine to lysine, thereby corroborating the overall findings of the computational model.

Amino Acid Motifs↗

PubMed2000

Size selectivity of narrow pores.

The selectivity of micropores and ion channels is examined for simple pore topologies within the framework of density functional theory of highly confined fluids. In an infinite cylindrical pore purely steric (excluded volume) effects are shown to lead to strong, nontrivial size selectivity, which is highly sensitive to the pore radius. A crude modeling of electrostatic effects does not alter the relative absorbance of Na+ and K+ ions in a significant way.

Ion Channels↗

PubMed2000

Constrained systems and statistical distribution

Theoretical advances in the statistical description of non-Hamiltonian systems [Tuckerman, Mundy, and Martyna, Europhys. Lett. 45, 149 (1999)] have recently led us to rethink the definition of the phase-space probability by using the proper invariant measure. Starting from this point of view, we will derive the statistical distribution of constrained systems, considered as non-Hamiltonian, in Cartesian coordinates, in a way independent from the standard Lagrangian treatment. Furthermore, we will analyze the statistical distribution of the Nose-Hoover isothermal (canonical or NVT) dynamics, considering with care the conservation laws hidden in the evolution equations. Consequently, we will correct the equations of motion in order to obtain the proper statistical ensemble. The isobaric-isothermal (constant pressure or NpT) form of the Nose-Hoover dynamics is then considered as a nontrivial extension of the described procedure and, similarly to the NVT case, we will correct the equations of motion with respect to previous versions. The case of a constrained system coupled to a thermostat and a piston is easily handled by means of the same formalism, whereas the Lagrangian treatment becomes involved.

Journal Article↗

PubMed2000

Enhanced sampling of rare events

We present a method to enhance sampling of a given reaction coordinate by projecting part of the random thermal noise along a preferential direction. The approach is promising to study rough energy landscapes and highly activated barriers that can be overcome by increasing the attempt frequency. Furthermore it allows us to rescale a given reaction coordinate without biasing the configurational properties of the system. A major advantage of the method is its simplicity in the analytical derivation and numerical implementation.

Journal Article↗

PubMed1999

Molecular dynamics simulations of Cu,Zn superoxide dismutase: effect of temperature on dimer asymmetry.

Molecular dynamics simulations of solvated dimeric Cu,Zn superoxide dismutase have been carried out at four temperatures, namely 200, 225, 250 and 300 K. Analysis of the backbone-to-backbone hydrogen bonds number indicates that the symmetry observed in the two subunits at 200 K is gradually lost by heating the system. The C(alpha) atoms displacement cross-correlation maps confirm that the asymmetric behaviour of the two subunits increases as a function of temperature. The dynamic cross-correlation of the subunits volumes indicates a fast correlation between the two subunits at 300 K, which is delayed upon lowering the simulation temperature. These results indicate that temperature plays an essential role in injecting such an asymmetry; the two subunits being asymmetric and in rapid communication at 300 K, and almost symmetric and in slow communication at lower temperatures.

Journal Article↗

PubMed1999

Origin of the low-frequency modes of globular proteins.

The incoherent structure factor associated with the nonexchangeable hydrogen atoms of carbomonoxy myoglobin at 80 and 200 K in a solvated sample has been computed from molecular dynamics simulations. The evaluated mean square displacements are almost three times larger than the experimental ones. However, the low-frequency band centered at 3 meV, observed in neutron scattering experiments, is reproduced. Evaluation of the contribution to the spectrum from different protein shells and backbone and side chain atoms allows us to propose that the low-frequency mode around 3 meV, which is a constant feature of all globular proteins, is mainly due to the hydrogen atoms belonging to the inner shell, suggesting that this mode is intrinsic to the protein itself.

Journal Article↗