Unfolding and melting of DNA (RNA) hairpins: the concept of structure-specific 2D dynamic landscapes.

A 2D free-energy landscape model is presented to describe the (un)folding transition of DNA/RNA hairpins, together with molecular dynamics simulations and experimental findings. The dependence of the (un)folding transition on the stem sequence and the loop length is shown in the enthalpic and entropic contributions to the free energy. Intermediate structures are well defined by the two coordinates of the landscape during (un)zipping.

Protein dynamics and stability: the distribution of atomic fluctuations in thermophilic and mesophilic dihydrofolate reductase derived using elastic incoherent neutron scattering.

The temperature dependence of the dynamics of mesophilic and thermophilic dihydrofolate reductase is examined using elastic incoherent neutron scattering. It is demonstrated that the distribution of atomic displacement amplitudes can be derived from the elastic scattering data by assuming a (Weibull) functional form that resembles distributions seen in molecular dynamics simulations. The thermophilic enzyme has a significantly broader distribution than its mesophilic counterpart.

Picosecond fluctuating protein energy landscape mapped by pressure temperature molecular dynamics simulation.

Microscopic statistical pressure fluctuations can, in principle, lead to corresponding fluctuations in the shape of a protein energy landscape. To examine this, nanosecond molecular dynamics simulations of lysozyme are performed covering a range of temperatures and pressures. The well known dynamical transition with temperature is found to be pressure-independent, indicating that the effective energy barriers separating conformational substates are not significantly influenced by pressure.

Lattice dynamics of a protein crystal.

All-atom lattice-dynamical calculations are reported for a crystalline protein, ribonuclease A. The sound velocities, density of states, heat capacity (C(V)) and thermal diffuse scattering are all consistent with available experimental data. C(V) proportional, variant T(1.

Protein dynamics from X-ray crystallography: anisotropic, global motion in diffuse scattering patterns.

Understanding X-ray crystallographic diffuse scattering is likely to improve our comprehension of equilibrium collective protein dynamics. Here, using molecular dynamics (MD) simulation, a detailed analysis is performed of the origins of diffuse scattering in crystalline Staphylococcal nuclease, for which the complete diffuse scattering pattern has been determined experimentally. The hydrogen-atom contribution and the scattering range over which the scattering can be considered to be a sum of solvent and protein scattering are determined.

Pressure-dependent transition in protein dynamics at about revealed by molecular dynamics simulation.

Molecular dynamics simulations of a crystalline protein, Staphylococcal nuclease, over the pressure range 1 bar to 15 kbar reveal a qualitative change in the internal protein motions at approximately 4 kbar. This change involves the existence of two linear regimes in the mean-square displacement for internal protein motion, (P) with a twofold decrease in the slope for P>4 kbar. The major effect of pressure on the dynamics is a loss, with increasing pressure of large amplitude, collective protein modes below 2 THz effective frequency, accompanied by restriction of large-scale solvent translational motion.

Correlated dynamics determining x-ray diffuse scattering from a crystalline protein revealed by molecular dynamics simulation.

The dynamical origin of the x-ray diffuse scattering by crystals of a protein, Staphylococcal nuclease, is determined using molecular dynamics simulation. A smooth, nearly isotropic scattering shell at originates from equal contributions from correlations in nearest-neighbor water molecule dynamics and from internal protein motions, the latter consisting of -helix pitch and inter--strand fluctuations. Superposed on the shell are intense, three-dimensional scattering features that originate from a very small number of slowly varying (>10 ns) collective motions.

Fluctuations and correlations in crystalline protein dynamics: a simulation analysis of staphylococcal nuclease.

Understanding collective motions in protein crystals is likely to furnish insight into functional protein dynamics and will improve models for refinement against diffraction data. Here, four 10 ns molecular dynamics simulations of crystalline Staphylococcal nuclease are reported and analyzed in terms of fluctuations and correlations in atomic motion. The simulation-derived fluctuations strongly correlate with, but are slightly higher than, the values derived from the experimental B-factors.

Understanding the energetics of helical peptide orientation in membranes.

Understanding the energetic factors determining the positioning and orientation of single-helical peptides in membranes is of fundamental interest in structural biology. Here, a simple 5-slab continuum dielectric model for the membrane is examined that distinguishes between the solvent, headgroup, and core regions. An analytical solution for the electrostatic solvation of a single dipole and an all-atom model of N-methylacetamide are used to demonstrate the effect of the dielectric boundaries in the system on peptide dipole orientation.

Analytic description of stochastic calcium-signaling periodicity.

Calcium release is an important tool for cellular signaling processes where chemical signals are converted into spatio-temporal variations of intracellular calcium concentration. We investigated the temporal behavior of a single cluster of inositol-(1,4,5)-triphosphate receptor (IP3R)-I channels and will present an analytic approach to obtain the spectrum of the calcium signal within the cluster. We compare these results with stochastic simulations and obtain an intermediate number of channels per cluster for optimal signaling periodicity.