Limitations of time-resolved fluorescence suggested by molecular simulations: assessing the dynamics of T cell receptor binding loops.

Time-resolved fluorescence anisotropy (TRFA) has a rich history in evaluating protein dynamics. Yet as often employed, TRFA assumes that the motional properties of a covalently tethered fluorescent probe accurately portray the motional properties of the protein backbone at the probe attachment site. In an extensive survey using TRFA to study the dynamics of the binding loops of a αß T cell receptor, we observed multiple discrepancies between the TRFA data and previously published results that led us to question this assumption. We thus simulated several of the experimentally probed systems using a protocol that permitted accurate determination of probe and protein time correlation functions. We found excellent agreement in the decays of the experimental and simulated correlation functions. However, the motional properties of the probe were poorly correlated with those of the backbone of both the labeled and unlabeled protein. Our results warrant caution in the interpretation of TRFA data and suggest further studies to ascertain the extent to which probe dynamics reflect those of the protein backbone. Meanwhile, the agreement between experiment and computation validates the use of molecular dynamics simulations as an accurate tool for exploring the molecular motion of T cell receptors and their binding loops.

The Langevin Hull: Constant pressure and temperature dynamics for non-periodic systems.

We have developed a new isobaric-isothermal (NPT) algorithm which applies an external pressure to the facets comprising the convex hull surrounding the system. A Langevin thermostat is also applied to the facets to mimic contact with an external heat bath. This new method, the "Langevin Hull", can handle heterogeneous mixtures of materials with different compressibilities. These systems are problematic for traditional affine transform methods. The Langevin Hull does not suffer from the edge effects of boundary potential methods, and allows realistic treatment of both external pressure and thermal conductivity due to the presence of an implicit solvent. We apply this method to several different systems including bare metal nanoparticles, nanoparticles in an explicit solvent, as well as clusters of liquid water. The predicted mechanical properties of these systems are in good agreement with experimental data and previous simulation work.

Breathing mode dynamics and elastic properties of gold nanoparticles.

We present calculations of the bulk modulus, heat capacity, and the period of the breathing mode for spherical nanoparticles following excitation by ultrafast laser pulses. The bulk modulus and heat capacities both exhibit clear transitions upon bulk melting of the particles. Equilibrium calculations of the heat capacity show that the melting transition is sharper and occurs at a lower temperature than one would observe from an ultrafast experiment. We also observe an intriguing splitting in the low-frequency spectra of the nanoparticles and analyze this splitting in terms of Lamb's classical theory of elastic spheres. We conclude that the particles either (1) melt during the observation period following laser excitation or (2) melt an outer shell while maintaining a crystalline core. Both mechanisms for melting are commensurate with our observations.

OOPSE: an object-oriented parallel simulation engine for molecular dynamics.

OOPSE is a new molecular dynamics simulation program that is capable of efficiently integrating equations of motion for atom types with orientational degrees of freedom (e.g. "sticky" atoms and point dipoles). Transition metals can also be simulated using the embedded atom method (EAM) potential included in the code. Parallel simulations are carried out using the force-based decomposition method. Simulations are specified using a very simple C-based meta-data language. A number of advanced integrators are included, and the basic integrator for orientational dynamics provides substantial improvements over older quaternion-based schemes.

Size-dependent spontaneous alloying of Au-Ag nanoparticles.

We report on systematic studies of size-dependent alloy formation of silver-coated gold nanoparticles (NPs) in aqueous solution at ambient temperature using X-ray absorption fine structure spectroscopy (XAFS). Various Au-core sizes (2.5-20 nm diameter) and Ag shell thicknesses were synthesized using radiolytic wet techniques. The equilibrium structures (alloy versus core-shell) of these NPs were determined in the suspensions. We observed remarkable size dependence in the room temperature interdiffusion of the two metals. The interdiffusion is limited to the subinterface layers of the bimetallic NPs and depends on both the core size and the total particle size. For the very small particles (< or =4.6 nm initial Au-core size), the two metals are nearly randomly distributed within the particle. However, even for these small Au-core NPs, the interdiffusion occurs primarily in the vicinity of the original interface. Features from the Ag shells do remain. For the larger particles, the boundary is maintained to within one monolayer. These results cannot be explained either by enhanced self-diffusion that results from depression of the melting point with size or by surface melting of the NPs. We propose that defects, such as vacancies, at the bimetallic interface enhance the radial migration (as well as displacement around the interface) of one metal into the other. Molecular dynamics calculations correctly predict the activation energy for diffusion of the metals in the absence of vacancies and show an enormous dependence of the rate of mixing on defect levels. They also suggest that a few percent of the interfacial lattice sites need to be vacant to explain the observed mixing.