Heterogeneous Nucleation of an n-Alkane on Tetrahedrally Coordinated Crystals.

Heterogeneous nucleation refers to the propensity for phase transformations to initiate preferentially on foreign surfaces, such as vessel walls, dust particles, or formulation additives. In crystallization, the form of the initial nucleus has ramifications for the crystallographic form, morphology, and properties of the resulting solid. Nevertheless, the discovery and design of nucleating agents remains a matter of trial and error because of the very small spatiotemporal scales over which the critical nucleus is formed and the extreme difficulty of examining such events empirically. Using molecular dynamics simulations, we demonstrate a method for the rapid screening of entire families of materials for activity as nucleating agents and for characterizing their mechanism of action. The method is applied to the crystallization of n-pentacontane, a model surrogate for polyethylene, on the family of tetrahedrally coordinated crystals, including diamond and silicon. A systematic variation of parameters in the interaction potential permits a comprehensive, physically based screening of nucleating agents in this class of materials, including both real and hypothetical candidates. The induction time for heterogeneous nucleation is shown to depend strongly on crystallographic registry between the nucleating agent and the critical nucleus, indicative of an epitaxial mechanism in this class of materials. Importantly, the severity of this registry requirement weakens with decreasing rigidity of the substrate and increasing strength of attraction to the surface of the nucleating agent. Employing this method, a high-throughput computational screening of nucleating agents becomes possible, facilitating the discovery of novel nucleating agents within a broad "materials genome" of possible additives.

Characterization of DNA conformation inside bacterial viruses.

In this study we develop a formalism to describe the organization of DNA inside bacteriophage capsids during genome packaging. We have previously shown that DNA inside bacteriophage phi29 (phi29) is organized into folded toroids [A. S. Petrov and S. C. Harvey, Structure 15, 21 (2007)], whereas epsilon15 (epsilon15) reveals the coaxial organization of the genetic material [A. S. Petrov, K. Lim-Hing, and S. C. Harvey, Structure 15, 807 (2007)]. We now show that each system undergoes two consecutive transitions. The first transition corresponds to the formation of global conformations and is analogous to a disorder-order conformational transition. The second transition is characterized by a significant loss of DNA mobility at the local level leading to glasslike dynamic behavior. Packing genetic material inside bacteriophages can be used as a general model to study the behavior of semiflexible chains inside confined spaces, and the proposed formalism developed here can be used to study other systems of linear polymer chains confined to closed spaces.

DNA organization and thermodynamics during viral packing.

An elastic DNA molecular mechanics model is used to compare DNA structures and packing thermodynamics in two bacteriophage systems, T7 and phi29. A discrete packing protocol allows for multiple molecular dynamics simulations of the entire packing event. In T7, the DNA is coaxially spooled around the cylindrical core protein, whereas the phi29 system, which lacks a core protein, organizes the DNA concentrically, but not coaxially. Two-dimensional projections of the packed structures from T7 simulations are consistent with cryo-electron micrographs of T7 phage DNA. The functional form of the force required to package the phi29 DNA is similar to forces determined experimentally, although the total free energy change is only 40% of the experimental value. Since electrostatics are not included in the simulations, this suggests that electrostatic repulsions are responsible for approximately 60% of the free energy required for packaging. The entropic penalty from DNA confinement has not been computed in previous studies, but it is often assumed to make a negligible contribution to the total work done in packing the DNA. Conformational entropy can be measured in our approach, and it accounts for 70-80% of the total work done in packing the elastic model DNA in both phages. For phi29, this corresponds to an entropic penalty of approximately 35% of the total work observed experimentally.

Folding behavior of model proteins with weak energetic frustration.

The native structure of fast-folding proteins, albeit a deep local free-energy minimum, may involve a relatively small energetic penalty due to nonoptimal, though favorable, contacts between amino acid residues. The weak energetic frustration that such contacts represent varies among different proteins and may account for folding behavior not seen in unfrustrated models. Minimalist model proteins with heterogeneous contacts--as represented by lattice heteropolymers consisting of three types of monomers--also give rise to weak energetic frustration in their corresponding native structures, and the present study of their equilibrium and nonequilibrium properties reveals some of the breadth in their behavior. In order to capture this range within a detailed study of only a few proteins, four candidate protein structures (with their cognate sequences) have been selected according to a figure of merit called the winding index--a characteristic of the number of turns the protein winds about an axis. The temperature-dependent heat capacities reveal a high-temperature collapse transition, and an infrequently observed low-temperature rearrangement transition that arises because of the presence of weak energetic frustration. Simulation results motivate the definition of a new measure of folding affinity as a sequence-dependent free energy--a function of both a reduced stability gap and high accessibility to non-native structures--that correlates strongly with folding rates.