Molecular dynamics simulations were conducted on a system consisting of a decamer DNA solvated by trehalose and water (molecular ratio= 1:2), to mimic a relatively dry state for the DNA molecule. Simulations were performed at two different temperatures, 300 K and 450 K. The B-form DNA structure was shown to be stable at both temperatures. The analysis of hydrogen bonds between trehalose/water and DNA revealed that trehalose and backbone DNA formed the largest number of hydrogen bonds and thus constituted the major effect of structural protection for DNA. The number of hydrogen bonds formed by each OH group of trehalose with the backbone DNA was compared. Different types of trehalose-DNA interactions were analyzed, with no prevalent pattern recognized. Diffusion constants for trehalose and water were also calculated, suggesting a glassy/viscose state of the simulation system. It is believed that trehalose protects DNA in the dry state through the network of hydrogen bonds built by the sugars, which reduces the structural fluctuations of DNA and prevents its denaturation.

Indiana University-Purdue University Indianapolis (IUPUI) / The cell membrane serves as a barrier between the interior and exterior of a living cell. Its main structural component is the lipid bilayer, which is composed of various kinds of lipids that segregate into domains. These lipid domains, distinguished in composition and physical properties from the bulk lipids that surround them, are believed to modulate the function of resident proteins by providing an appropriate lipid environment. Polyunsaturated fatty acids (PUFA) are a type of fatty acid that contain multiple C=C double bonds. They have a lot of health benefits, which may originate in part due to their incorporation into lipids in the plasma membrane. Hypotheses that PUFA-containing lipids laterally separate into domains and/or modulate the structure of existing domains have been raised to explain the fundamental role played by PUFA. In our research, we use molecular dynamics (MD) simulations to simulate model membranes composed of PUFA-containing phospholipids and to investigate their interaction with cholesterol and vitamin E that are influential membrane constituents. The presumptive function for vitamin E in membranes is to protect PUFA against oxidation. Although the chemistry of the process is well established, the role played by the molecular structure that we address with atomistic molecular dynamics (MD) simulations remains controversial. We compared the behavior of vitamin E in lipid bilayers composed of 1-stearoyl-2-docosahexaenoylphosphatidylcholine (SDPC, 18:0-22-6PC) and 1-stearoyl-2-oleoylphosphatidylcholine (SOPC, 18:0-18:1PC) via all-atom MD simulations at 37° C. SDPC represents a PUFA-containing lipid, and SOPC serves as monounsaturated control. From the calculation of van der Waals energy of interaction between vitamin E and fatty acid (FA) chains, we found higher probability that the PUFA chains surround the chromanol head group on vitamin E. This is further demonstrated by probability density maps of acyl chains around vitamin E molecules. Also, an ability to more easily penetrate deep into the PUFA containing bilayer of vitamin E is detected by faster flip-flop rate of vitamin E observed in the SDPC bilayers. These results showed that the high disorder of polyunsaturated docosahexaenoic acid (DHA) chains allows vitamin E to easily tunnel down into the bilayer and often brings the PUFA chains up to the surface of the bilayer, improving the likelihood that the reactive (hydroxyl) group on vitamin E would encounter a lipid peroxyl radical and terminate the oxidation process. Thus, the simulations indicate that the molecular structure of vitamin E supports its role as an antioxidant in a PUFA-containing membrane. A subsequent study on the partitioning of vitamin E into PUFA-containing lipids was done by analyzing the binding energy of vitamin E in the corresponding lipid bilayer. The binding energy is obtained from the potential of mean force (PMF) profile of vitamin E alone the membrane normal direction (z), which is calculated from umbrella sampling MD simulations. We found the binding in SDPC is smaller in SOPC, indicating that vitamin E does not prefer PUFA-containing phospholipids. The flip-flop rate was also estimated from the PMF profile, confirming that vitamin E flip-flops across the SDPC bilayer more easily than the SOPC bilayer. From the simulations it was noted that the membrane deforms as vitamin E is pulled out, which suggests interactions between the phospholipids contribute to the binding energy of the vitamin E. In a final study, a comparison was made between the effect on membrane organization of the three types of long chain omega-3 (n-3) PUFA found in fish oils: eicosapentaenoic acid (EPA, 20:5), DHA (22:6) and docosapentaenoic acid (DPA, 22:5). MD simulations were run on lipid bilayers composed of 1-stearoyl-2-eicosapentaenoylphosphatidylcholine (EPA-PC, 18:0-20:5PC), 1-stearoyl-2-docosapentaenoylphosphatidylcholine (DPA-PC, 18:0-22:5PC), SDPC (DHA-PC, 18:0-22:6PC) and, as a monounsaturated control, SOPC (OA-PC, 18:0-18:1PC) in the absence and presence of cholesterol. By analyzing the physical properties such as membrane order and thickness, we found all three n-3 PUFAs disorder the membrane. The disordering is greatest with EPA and least with DPA. Unique among the n-3 PUFA-containing membranes, there is region of high order in the upper portion of the DPA chain. The PUFA-containing lipids were found to less favorably interact with cholesterol compared to the OA-containing lipid, which is caused by their disorder. We speculate that differences between DPA, DHA and EPA might potentially modulate their effect on lipid domain formation.

No description available.

Molecular dynamics simulation and density functional theory were applied to calculate heats of immersion (Himm) of n-heptane, toluene, pyridine and water on two model sand surfaces and two model clay surfaces. Our results indicated that water showed the highest Himm for the model clay surfaces when multi-molecular water layers were used but the lowest when a single molecular layer was used. Simulations of a single molecular water layer sandwiched between a single molecular layer of the aforementioned organic compounds and the octahedral surface of clay indicated that the water layer was not stable. In particular, water molecules tended to desorb from the surface and clustered together to form water/water hydrogen bonds. Given the nature of bitumen molecules, the current results support the hypothesis that a pre-existing water layer on the sand and clay surfaces in raw oil sands is plausible so long as it is thick enough. / Chemical Engineering

<p>  </p> <p>Architectured metamaterials are artificial systems with unique structural characteristics. They show distinct deformation behaviors and improved mechanical properties compared to regular materials. For example, mechanical metamaterials demonstrate negative Poisson's ratios, whereas regular materials have positive values. In theory, the auxetic behaviors arise from periodic cellular architectures regardless of the materials utilized. While this premise is mostly true for macroscopic metamaterials, it may not work well at a very small lengthscale since chemistry may play a critical role in nanostructures. However, this fundamental idea has not been addressed due to the lack of powerful manufacturing strategies at the nanoscale. The majority of architectured metamaterials are manufactured from top down with their unit size of microns or larger. On the other hand, there are also molecular auxetics which are natural crystals and thus are not designable. Therefore, there is a significant gap in lengthscale from 10 nm to 1 µm. DNA self-assembly is a bottom-up approach that can construct complex nanostructures based on sequence complementarity. Examples include DNA origami structures and DNA tile assemblies. This dissertation bridges the gap in the lengthscale by introducing nanoscale auxetic units from DNA and investigates relevant structural properties and mechanical behaviors. This study addresses the premise of metamaterials and elucidates the structure-property relation. The findings from this work formulate design principles for DNA based auxetic metastructures. </p> <p>In this work, we built several two-dimensional (2D) auxetic nanostructures from wireframe DNA origami. They serve as the model systems to demonstrate the feasibility of constructing nanoscale auxetics via DNA self-assembly. DNA origami structures are commonly constructed by a long ‘scaffold’ strand with many ‘staple’ oligonucleotides. Since the DNA metastructures are too small to directly apply external forces, we implemented chemical deformation by inserting ‘jack’ edges. Like a car jack, the length of the jack edges can be modulated via two-step DNA reactions: toehold-mediated strand displacement and annealing with a new set of jack staples. The DNA nanostructures reconfigure accordingly. To complement the experiment, we performed molecular dynamics (MD) simulations based on coarse-grained models using an open-source oxDNA platform. In the numerical computation, external loads were directly applied to deform the metastructures, providing details of structural deformation. We discovered that the auxetic behaviors of DNA metamaterials can be estimated by architectural designs, however the material properties are also crucial in the structures and deformations. Our mechanistic study provided general design guidelines for 2D auxetic DNA metamaterials. We also designed and constructed a Hoberman flight ring from DNA, a simplified planar version of Hoberman sphere. This structure consists of six equilateral triangles that are topologically organized into two layers, resembling a trefoil knot. The DNA flight ring deploys upon external forces, expanding (open state) or contracting (closed state) by sliding the two layers of triangles. This is the first synthetic deployable nanostructure and offers a versatile platform for topological research.</p> <p>This thesis also investigates 3D effects in DNA assemblies and related mechanics. We used a DNA origami tile designed with an intrinsic twist as a model system and explored its cyclization process using MD simulations. The numerical computation revealed the detailed process where the structure untwists and curves for cyclization simultaneously under external forces. The force and energy required to overcome the initial curvature and cause the 3D deformation were also calculated. The results agree well with the previous experiment and theory, further verifying the simulation method. Direct mechanical forces and DNA responses were realized experimentally with 3D DNA crystals built from triangular DNA tiles. Nanoindentation was performed on macroscopic ligated crystals using atomic force microscopy (AFM). MD simulations were performed in parallel, which revealed the full spectrum of several distinct deformation modes from linear elasticity to structural failure. The combined experiment, computation, and theoretical calculation showed that the complex behaviors can only be understood fully by considering the structure and its components. </p> <p>The scientific findings from this thesis should contribute to the construction of auxetic metastructures, the design methods for DNA based metamaterials as well as the prediction of their structural properties and mechanical behaviors. This thesis will pave the way for building architectured materials from DNA with tailored properties and functionalities, opening the door for new opportunities and unique applications.</p>

No / D-amino acids are useful building blocks for de novo peptide design and they play a role in aging-related diseases associated with gradual protein racemization. For amino acids with achiral side chains, one should be able to presume that the conformational propensities of L- and D-amino acids are a reflection of one another due to the straightforward geometric inversion at the Cα atom. However, this presumption does not account for the directionality of the backbone dipole and the inverted propensities have never been definitively confirmed in this context. Furthermore, there is little known of how alternative side chain chirality affects the backbone conformations of isoleucine and threonine. Using a GGXGG host-guest pentapeptide system, we have completed exhaustive sampling of the conformational propensities of the D-amino acids, including D-allo-isoleucine and D-allo-threonine, using atomistic molecular dynamics simulations. Comparison of these simulations with the same systems hosting the cognate L-amino acids verifies that the intrinsic backbone conformational propensities of the D-amino acids are the inverse of their cognate L-enantiomers. Where amino acids have a chiral center in their side chain (Thr, Ile) the β-configuration affects the backbone sampling, which in turn can confer different biological properties. / NIH

On Cu(111) surface and in interaction with a single hexa-tert-butylphenylbenzene moleculegear, the rotation of a graphene nanodisk was studied using the large-scale atomic/molecular massively parallel simulator molecular dynamics simulator. To ensure a transmission of rotation to the molecule-gear, the graphene nanodisk is functionalized on its circumference by tertbutylphenyl chemical groups. The rotational motion can be categorized underdriving, driving and overdriving regimes calculating the locking coefficient of this mechanical machinery as a function of external torque applied to the nanodisk. The rotational friction with the surface of both the phononic and electronic contributions is investigated. For small size graphene nanodisks, the phononic friction is the main contribution. Electronic friction dominates for the larger disks putting constrains on the experimental way of achieving the transfer of rotation from a graphene nanodisk to a single molecule-gear.

Doctor of Philosophy / Department of Chemistry / Paul E. Smith / The force fields used in computer simulations play an important role in describing a particular system. In order to estimate the accuracy of a force field, physical or thermodynamic properties are usually compared with simulation results. Recently, we have been developing a force field which is called the Kirkwood-Buff Force Field (KBFF). This force field is established by transforming experimental data into Kirkwood-Buff (KB) integrals and then attempting to reproduce those KBIs with molecular dynamic (MD) simulations. Here we investigate a variety of intermolecular interactions in aqueous solutions through KB theory and molecular simulations. First, we describe a force field for the simulation of alkali halide aqueous solutions. These models are developed specifically to reproduce the experimentally determined Kirkwood-Buff integrals and solution activities as a function of molality. Additionally, other experimentally known properties including ion diffusion constants, relative permittivities, the densities and heats of mixing are reproduced by these models. Second, In an effort to understand the interactions which occur between amino acids in solution we have developed new force fields for simple amino acids and their analogs including glycine, betaine, β-alanine, dl-alanine, NH4Cl, NH4Br, N(CH3)4Cl, N(CH3)4Br, CH3NH3Cl, and CH3COONa. The new force fields reproduce the experimental Kirkwood-Buff integrals which describe the relative distribution of all the species in a solution mixture. Furthermore, it is shown that these simple amino acids can be understood in terms of the interactions of their functional groups and that, to a very good approximation, the transferability and additivity usually assumed in the development of biomolecular force fields appear to hold true. Third, an analysis of the effect of a cosolvent on the association of a solute in solution is presented by using the Kirkwood-Buff theory of solutions. The derived expressions provide a foundation for the investigation of cosolvent effects on molecular and biomolecular equilibria, including protein association, aggregation, and cellular crowding. Finally, in an effort to understand peptide aggregation at the atomic level we have performed simulations of polyglycine ((gly)n) using our recently developed force fields. Experimentally, the association of glycine polypeptides increases with n. Our force fields reproduce this behavior, and we investigated the reasons behind this trend. In addition to studying closed ensembles, we also simulate these systems in a semi-open ensemble that was designed to mimic cellular environments typically open to water, using a simple direct approach. The differences between the two ensembles are investigated and compared with our recent theoretical descriptions of aggregating systems using Kirkwood-Buff theory.

Recently there has been a great deal of attention in the oilfield industry focused on the phenomenal properties of viscoelastic surfactants (VES). The interest is motivated by their applications as switchable smart fluids, their surface tension, and their thickening and rheology enhancement in aqueous solution. Surfactant molecules in solution are known for their ability to assemble spontaneously into complex structures. Under certain thermodynamic conditions, temperature and electrolyte concentrations, wormlike micelles are formed. These micelles share similar equilibrium and dynamic properties with polymer solutions, However, micellar chains can break and recombine spontaneously which make them part of the more general class of living polymers. It is vital to understand the properties of viscoelastic wormlike micelles with regard to their flow in porous media. The overall objective of this study is to establish a better understanding of counterion effect on behavior of VES. The dependence of macroscopic properties on intermolecular interactions of complex fluid systems such as VES is an enormous challenge. To achieve our objective, we use first-principle calculations and molecular dynamics (MD) simulations to resolve the full chemical details in order to study how the structure of the micellar and solution properties depends on the chemical structure of the surfactant head group (HG) and type of counterion. In particular, we run simulations for different structures in gas-phase and aqueous solutions together with their salt counterions at room temperature and atmospheric pressure. For this purpose, we consider four types of surfactant HG (anionic, cationic, betaine and amidoamine oxide) together with the most common ions present in the acidizing fluid of a carbonate reservoir such as Ca2+, Mg2+, Fe2+, Fe3+, Mn2+ and Zn2+, Cl-, OH- and HS-. Hydration of ions as well as interactions with surfactant the HG are studied using density functional theory (DFT). The results give important insight into the links between molecular details of VES HG structure and observed solution properties. This study proposes for the first time the possible mechanisms that explain the exotic behavior of VES at high Fe(III) concentration. Also, our MD simulation suggests that distribution of chloride ion around surfactant molecules is responsible for their viscosity behavior in HCl solution. We believe that our results are an important step to develop more systematic procedures for the molecular design and formulation of more effective and efficient VES systems.

RNA tetraloop is the smallest, simplest and the most frequent motif which is involved in numerous important biological functions. A local deviation from the RNA standard tetraloop, d2 tetraloop, has been identified with high abundance in 5S, 16S and 23S rRNAs. The presence of d2 tetraloops in highly conserved regions of 16S and 23S rRNAs suggests their functional importance. With one less residue in the loop, d2 tetraloops are considered more energetically restrained and less stable than standard tetraloops. The deletion at position j+2 in the loop is always correlated with adjacent stem distortion. MD simulations of 314-d2-tetraloop (a sample structure of d2 tetraloops) and cutd2-tetraloop (an artificially built perfect d2 tetraloop with no stem defects) have shown that stem defects are the stabilizing factor of d2 tetraloops. Simulations have also revealed that the insertion residue 318C (an example of stem defect) is stabilizing 314-d2-tetraloop by forming hydrogen bonding interactions with both the loop and the stem. When these two hydrogen bonding interactions are eliminated, the structure remained relatively stable compared to cutd2-tetraloop where the insertion residue was completely removed from the stem. This suggests the insertion residue is also stabilizing 314-d2-tetraloop by providing some conformational relaxation in the stem. Investigation of RNA standard tetraloop high temperature unfolding has revealed that the d2 tetraloop is possibly a kinetically trapped intermediate state during the folding of the standard tetraloop. High temperature unfolding simulations of standard tetraloop have shown a three-state folding behavior: a folded state, an intermediate state and an unfolded state. The folding of standard tetraloop starts with the formation of the loop. The closing base pair forms first, followed by the loop and the stem which form critical interactions such as base pairing and stacking that make a tetraloop. ROMP PNB has been investigated as supports to immobilize homogeneous catalysts to achieve both high reactivity and selectivity and easy separation. Polymers with intermediate conformational order can increase the accessibility of tethered homogeneous catalysts. Simulations of ROMP PNBDC_UD have shown the importance of bulky side groups in enabling the polymer to adopt a helical conformation. Such helical conformations have been associated with intermediate structural order in similar polymers such as PNB made by non-ROMP mechanisms. This intermediate order manifests itself as a split in the amorphous halo of WAXD pattern. Bulk simulations generated WAXD patterns that are close to the experimentally generated WAXD patterns where there are two split peaks: lower angle peak representing intermolecular interaction and higher angle peak representing intramolecular interaction.