The Replica Exchange Statistical Temperature Molecular Dynamics algorithm is used to study the equilibrium properties of a peptide monomer and dimer and the thermodynamics of peptide dimer formation. The simulation data are analyzed by the Statistical Temperature Weighted Histogram Analysis Method. Each 10-residue peptide is represented by a coarse-grained model with hydrophobic side chains and has an α-helix as its minimum energy configuration. It is shown that the configurational behavior of the dimer can be divided into four regions as the temperature increases: two folded peptides; one folded and one unfolded peptide; two unfolded peptides; and two spatially separated peptides. Two important phenomena are discussed: in the dimer, one peptide unfolds at a lower temperature than the isolated monomer and the other peptide unfolds at a higher temperature than the isolated monomer. In addition, in the temperature region where one peptide is folded and the other unfolded, the unfolded peptide adopts an extended structure that minimizes the overall surface area of the aggregate. It is suggested that combination of destabilization due to aggregation and the resulting extended configuration of the destabilized peptide could have implications for nucleating β-sheet structures and the ultimate formation of fibrils.

Polyaromatic dye molecules employed in photovoltaic and electronic applications are often processed in organic solvents. The aggregation of these dyes is key to their applications, but a fundamental molecular understanding of how the solvent environment controls the stacking of polyaromatics is unclear. This study reports initial results from Monte Carlo simulations of how various acene molecule dimers stack when they are dissolved in different solvents. Free energies computed using full dispersion interactions versus those with sterics only suggest that solvent entropy alone accounts for the majority of the stacking free energy in solvents with compact molecular geometries such as carbon tetrachloride. However, in contrast with carbon tetrachloride, we also observe significant variations in the stacking free energies of naphthalene, anthracene, and tetracene across other solvents such as toluene and cyclohexane. The weak attractive dispersion interactions between the acene solutes and planar and near-planar solvent molecules enable them to intercalate between the acene monomers, inducing extra stability beyond what solvent entropic driving force alone could predict. In all three solvents studied (carbon tetrachloride, cyclohexane, toluene) the solvent environment helps facilitate stacking of all three acenes studied (naphthalene, anthracene, tetracene), inducing a significant stabilization free energy between −4 and −8 kcal/mol. Extensive free energy umbrella sampling along the other orthogonal directions allows us to accurately calculate the dimerization equilibrium constants of all three acenes, which vary over several orders of magnitude in a way that depends intricately on the solvent they are in. Given the prevalence of solution-based processing techniques for organic electronic and photonic devices, these results provide useful insights into the critical role that solvent structure and characteristics play in the solution-based aggregation of organic dyes.

permutation on the protein chain can give important information about the connectivity, structure and folding or unfolding kinetics which guides its translocation and subsequent function in the cell. To study the process of cotranslocational unfolding and its dependence on the secondary structure at the N-terminus of the protein imported, we conduct a comparative molecular dynamics study of circular permutants of Dihydrofolate reductase(DHFR) using atomistic model in CHARMM. Six Circular Permutants -CP25, CP38, CP78, CP97, CP108, CP133 -are generated such that the new N-terminus leads either to an alpha helix or a beta-strand. using Steered Molecular Dynamics we compute the work distributions for the forced unfolding of each of the CP's and native DHFR using two processes -unfolding through the geometrical constriction of the model pore as in mitochondrial translocation and mechanical unfolding with the C-terminus fixed. In both cases the unfolding force is applied at the N-terminus. A comparison of the free energy profile along the reaction coordinate for each circular permutant can lead to identification of different unfolding pathways and hence import efficiency based on first resistant structure adjacent to the targeting sequence. 2053-Pos Board B72Design of Structral Metal Sites in Heterospecific Collagen Peptides Avanish S. Parmar, Fei Xu, Douglas pike, Vikas Nanda. UMDNJ, Piscataway, NJ, USA. Globular proteins commonly use structural metals to promote folding and enhance stability. There are no good examples of similar metal utilization in fibrillar proteins such as collagen. We hypothesized a metal binding site at the end of an A:B:C-type collagen triple helix could be designed to enhance folding and stability without compromising specificity. A heterospecific metal binding site was computationally designed by sampling backbone and sidechain conformations of C-terminal amino acids of the triple helix to optimize metal site geometry. Experimental characterization of the designed sequences confirms that zinc-binding enhances structure and thermal stability of the A:B:C heterotrimer peptides under physiological buffer conditions. By varying metal concentration, it is possible to study the relative contributions of electrostatic interactions and metal binding, to triple helix stability and structure. Metal-directed switching of triple helical structure has potential applications in self-assembly of higher order biomaterials, translational regenerative medicine and drug design. 2054-Pos Board B73Aromatic Amino Acids Confer Folding Propensities to a Nine-Residue Peptide We investigated how individual amino acids affect the structural propensities of short peptides. We based our work on NMR measurements of peptides of sequence EGAAXAASS, where 15 different amino acids were tested at position X. Here we focus on the two peptides with X = Trp and Gly, especially on their residual dipolar couplings (RDC). The pattern of the peptide with X = Gly was rather flat, suggesting an extended or unfolded peptide, while the ...

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