Using computational fluid dynamics in combating erosion-corrosion

Computational fluid dynamics was used to search for the links between the observed pattern of attack seen in a bauxite refinery's heat exchanger headers and the hydrodynamics inside the header. Validation of the computational fluid dynamics results was done by comparing then with flow parameters measured in a 1:5 scale model of the first pass header in the laboratory. Computational fluid dynamics simulations were used to establish hydrodynamic similarity between the 1:5 scale and full scale models of the first pass header. It was found that the erosion-corrosion damage seen at the tubesheet of the first pass header was a consequence of increased levels of turbulence at the tubesheet caused by a rapidly turning flow. A prismatic flow corrections device introduced in the past helped in rectifying the problem at the tubesheet but exaggerated the erosion-corrosion problem at the first pass header shell. A number of alternative flow correction devices were tested using computational fluid dynamics. Axial ribbing in the first pass header and an inlet flow diffuser have shown the best performance and were recommended for implementation. Computational fluid dynamics simulations have revealed a smooth orderly low turbulence flow pattern in the second, third and fourth pass as well as the exit headers where no erosion-corrosion was seen in practice. This study has confirmed that near-wall turbulence intensity, which can be successfully predicted by using computational fluid dynamics, is a good hydrodynamic predictor of erosion-corrosion damage in complex geometries. (c) 2006 Published by Elsevier Ltd.

Implementation of particle-scale rotation in the 3-d Lattice Solid Model

In this study, 3-D Lattice Solid Model (LSMearth or LSM) was extended by introducing particle-scale rotation. In the new model, for each 3-D particle, we introduce six degrees of freedom: Three for translational motion, and three for orientation. Six kinds of relative motions are permitted between two neighboring particles, and six interactions are transferred, i.e., radial, two shearing forces, twisting and two bending torques. By using quaternion algebra, relative rotation between two particles is decomposed into two sequence-independent rotations such that all interactions due to the relative motions between interactive rigid bodies can be uniquely decided. After incorporating this mechanism and introducing bond breaking under torsion and bending into the LSM, several tests on 2-D and 3-D rock failure under uni-axial compression are carried out. Compared with the simulations without the single particle rotational mechanism, the new simulation results match more closely experimental results of rock fracture and hence, are encouraging. Since more parameters are introduced, an approach for choosing the new parameters is presented.

Characterization of the structure of RAMP1 by mutagenesis and molecular modeling

Receptor activity modifying proteins (RAMPs) are a family of single-pass transmembrane proteins that dimerize with G-protein-coupled receptors. They may alter the ligand recognition properties of the receptors (particularly for the calcitonin receptor-like receptor, CLR). Very little structural information is available about RAMPs. Here, an ab initio model has been generated for the extracellular domain of RAMP1. The disulfide bond arrangement (Cys 27-Cys82, Cys40-Cys72, and Cys 57-Cys104) was determined by site-directed mutagenesis. The secondary structure (a-helices from residues 29-51, 60-80, and 87-100) was established from a consensus of predictive routines. Using these constraints, an assemblage of 25,000 structures was constructed and these were ranked using an all-atom statistical potential. The best 1000 conformations were energy minimized. The lowest scoring model was refined by molecular dynamics simulation. To validate our strategy, the same methods were applied to three proteins of known structure; PDB:1HP8, PDB:1V54 chain H (residues 21-85), and PDB:1T0P. When compared to the crystal structures, the models had root mean-square deviations of 3.8 Å, 4.1 Å, and 4.0 Å, respectively. The model of RAMP1 suggested that Phe93, Tyr 100, and Phe101 form a binding interface for CLR, whereas Trp74 and Phe92 may interact with ligands that bind to the CLR/RAMP1 heterodimer. © 2006 by the Biophysical Society.

Identifying and correcting non-Markov states in peptide conformational dynamics

Conformational transitions in proteins define their biological activity and can be investigated in detail using the Markov state model. The fundamental assumption on the transitions between the states, their Markov property, is critical in this framework. We test this assumption by analyzing the transitions obtained directly from the dynamics of a molecular dynamics simulated peptide valine-proline-alanine-leucine and states defined phenomenologically using clustering in dihedral space. We find that the transitions are Markovian at the time scale of ˜ 50 ps and longer. However, at the time scale of 30–40 ps the dynamics loses its Markov property. Our methodology reveals the mechanism that leads to non-Markov behavior. It also provides a way of regrouping the conformations into new states that now possess the required Markov property of their dynamics.

Water-peptide dynamics during conformational transitions

Transitions between metastable conformations of a dipeptide are investigated using classical molecular dynamics simulation with explicit water molecules. The distribution of the surrounding water at different moments before the transitions and the dynamical correlations of water with the peptide's configurational motions indicate that the water molecules represent an integral part of the molecular system during the conformational changes, in contrast to the metastable periods when water and peptide dynamics are essentially decoupled.

Non-Markov state model of peptide dynamics

A hidden Markov state model has been applied to classical molecular dynamics simulated small peptide in explicit water. The methodology allows increasing the time resolution of the model and describe the dynamics with the precision of 0.3 ps (comparing to 6 ps for the standard methodology). It also permits the investigation of the mechanisms of transitions between the conformational states of the peptide. The detailed description of one of such transitions for the studied molecule is presented. © 2012 Elsevier B.V. All rights reserved.

Multiscale modelling:approaches and challenges

Multiscale systems that are characterized by a great range of spatial–temporal scales arise widely in many scientific domains. These range from the study of protein conformational dynamics to multiphase processes in, for example, granular media or haemodynamics, and from nuclear reactor physics to astrophysics. Despite the diversity in subject areas and terminology, there are many common challenges in multiscale modelling, including validation and design of tools for programming and executing multiscale simulations. This Theme Issue seeks to establish common frameworks for theoretical modelling, computing and validation, and to help practical applications to benefit from the modelling results. This Theme Issue has been inspired by discussions held during two recent workshops in 2013: ‘Multiscale modelling and simulation’ at the Lorentz Center, Leiden (http://www.lorentzcenter.nl/lc/web/2013/569/info.php3?wsid=569&venue=Snellius), and ‘Multiscale systems: linking quantum chemistry, molecular dynamics and microfluidic hydrodynamics’ at the Royal Society Kavli Centre. The objective of both meetings was to identify common approaches for dealing with multiscale problems across different applications in fluid and soft matter systems. This was achieved by bringing together experts from several diverse communities.

Molecular alignment relaxation in polymer optical fibers for sensing applications

A systematic study of annealing behavior of drawn PMMA fibers was performed. Annealing dynamics were investigated under different environmental conditions by fiber longitudinal shrinkage monitoring. The shrinkage process was found to follow a stretched exponential decay function revealing the heterogeneous nature of the underlying molecular dynamics. The complex dependence of the fiber shrinkage on initial degree of molecular alignment in the fiber, annealing time and temperature was investigated and interpreted. Moreover, humidity was shown to have a profound effect on the annealing process, which was not recognized previously. Annealing was also shown to have considerable effect on the fiber mechanical properties associated with the relaxation of molecular alignment in the fiber. The consequences of fiber annealing for the climatic stability of certain polymer optical fiber-based sensors are discussed, emphasizing the importance of fiber controlled pre-annealing with respect to the foreseeable operating conditions.

Pressure induced structural changes and gas diffusion pathways in monomeric fluorescent proteins

Fluorescent proteins (FPs) are extremely valuable biochemical markers which have found a wide range of applications in cellular and molecular biology research. The monomeric variants of red fluorescent proteins (RFPs), known as mFruits, have been especially valuable for in vivo applications in mammalian cell imaging. Fluorescent proteins consist of a chromophore caged in the beta-barrel protein scaffold. The photophysical properties of an FP is determined by its chromophore structure and its interactions with the protein barrel. Application of hydrostatic pressure on FPs results in the modification of the chromophore environment which allows a systematic study of the role of the protein-chromophore interactions on photophysical properties of FPs. Using Molecular Dynamics (MD) computer simulations, I investigated the pressure induced structural changes in the monomeric variants mCherry, mStrawberry, and Citrine. The results explain the molecular basis for experimentally observed pressure responses among FP variants. It is found that the barrel flexibility, hydrogen bonding interactions and chromophore planarity of the FPs can be correlated to their contrasting photophysical properties at vaious pressures. I also investigated the oxygen diffusion pathways in mOrange and mOrange2 which exhibit marked differences in oxygen sensitivities as well as photostability. Such computational identifications of structural changes and oxygen diffusion pathways are important in guiding mutagenesis efforts to design fluorescent proteins with improved photophysical properties.

Docking and simulation study of the enantiospecificity of chiral epoxidation reactions catalyzed by chloroperoxidase

Chloroperoxidase (CPO), a 298-residue glycosylated protein from the fungus Caldariomyces fumago, is probably the most versatile heme enzyme yet discovered. Interest in CPO as a catalyst is based on its power to produce enantiomerically enriched products. Recent research has focused its attention on the ability of CPO to epoxidize alkenes in high regioselectivity and enantioselectivity as an efficient and environmentally benign alternative to traditional synthetic routes. There has been little work on the nature of ligand binding, which probably controls the regio- and enantiospecifity of CPO. Consequently it is here that we focus our work. We report docking calculations and computer simulations aimed at predicting the enantiospecificity of CPO-catalyzed epoxidation of three model substrates. On the basis of this work candidate mutations to improve the efficiency of CPO are predicted. In order to accomplish these aims, a simulated annealing and molecular dynamics protocol is developed to sample potentially reactive substrate/CPO complexes.

Stable algorithm for event detection in event-driven particle dynamics : logical states

Acknowledgments The authors gratefully acknowledge the support of the German Research Foundation (DFG) through the Cluster of Excellence ‘Engineering of Advanced Materials’ at the University of Erlangen-Nuremberg and through Grant Po 472/25.

Interdigitating organic bilayers direct the short interlayer spacing in hybrid organic–inorganic layered vanadium oxide nanostructures

Layered metal oxides provide a single-step route to sheathed superlattices of atomic layers of a variety of inorganic materials, where the interlayer spacing and overall layered structure forms the most critical feature in the nanomaterials’ growth and application in electronics, health, and energy storage. We use a combination of computer simulations and experiments to describe the atomic-scale structure, dynamics and energetics of alkanethiol-intercalated layered vanadium oxide-based nanostructures. Molecular dynamics (MD) simulations identify the unusual substrate-constrained packing of the alkanethiol surfactant chains along each V2O5 (010) face that combines with extensive interdigitation between chains on opposing faces to maximize three-dimensional packing in the interlayer regions. The findings are supported by high resolution electron microscopy analyses of synthesized alkanethiol-intercalated vanadium oxide nanostructures, and the preference for this new interdigitated model is clarified using a large set of MD simulations. This dependency stresses the importance of organic–inorganic interactions in layered material systems, the control of which is central to technological applications of flexible hybrid nanomaterials.

Insight into the mechanism of galactokinase: role of a critical glutamate residue and helix/coil transitions

Galactokinase, the enzyme which catalyses the first committed step in the Leloir pathway, has attracted interest due to its potential as a biocatalyst and as a possible drug target in the treatment of type I galactosemia. The mechanism of the enzyme is not fully elucidated. Molecular dynamics (MD) simulations of galactokinase with the active site residues Arg-37 and Asp-186 altered predicted that two regions (residues 174-179 and 231-240) had different dynamics as a consequence. Interestingly, the same two regions were also affected by alterations in Arg-105, Glu-174 and Arg- 228. These three residues were identified as important in catalysis in previous computational studies on human galactokinase. Alteration of Arg-105 to methionine resulted in a modest reduction in activity with little change in stability. When Arg-228 was changed to methionine, the enzyme’s interaction with both ATP and galactose was affected. This variant was significantly less stable than the wild-type protein. Changing Glu-174 to glutamine (but not to aspartate) resulted in no detectable activity and a less stable enzyme. Overall, these combined in silico and in vitro studies demonstrate the importance of a negative charge at position 174 and highlight the critical role of the dynamics in to key regions of the protein. We postulate that these regions may be critical for mediating the enzyme’s structure and function. 

Coarse Graining to Invesitigate Peptide-Lipid Interactions

Experimental characterization of molecular details is challenging, and although single molecule experiments have gained prominence, oligomer characterization remains largely unexplored. The ability to monitor the time evolution of individual molecules while they self assemble is essential in providing mechanistic insights about biological events. Molecular dynamics (MD) simulations can fill the gap in knowledge between single molecule experiments and ensemble studies like NMR, and are increasingly used to gain a better understanding of microscopic properties. Coarse-grained (CG) models aid in both exploring longer length and time scale molecular phenomena, and narrowing down the key interactions responsible for significant system characteristics. Over the past decade, CG techniques have made a significant impact in understanding physicochemical processes. However, the realm of peptide-lipid interfacial interactions, primarily binding, partitioning and folding of amphipathic peptides, remains largely unexplored compared to peptide folding in solution. The main drawback of existing CG models is the inability to capture environmentally sensitive changes in dipolar interactions, which are indigenous to protein folding, and lipid dynamics. We have used the Drude oscillator approach to incorporate structural polarization and dipolar interactions in CG beads to develop a minimalistic peptide model, WEPPROM (Water Explicit Polarizable PROtein Model), and a lipid model WEPMEM (Water Explicit Polarizable MEmbrane Model). The addition of backbone dipolar interactions in a CG model for peptides enabled us to achieve alpha-beta secondary structure content de novo, without any added bias. As a prelude to studying amphipathic peptide-lipid membrane interactions, the balance between hydrophobicity and backbone dipolar interactions in driving ordered peptide aggregation in water and at a hydrophobic-hydrophilic interface, was explored. We found that backbone dipole interactions play a crucial role in driving ordered peptide aggregation, both in water and at hydrophobic-hydrophilic interfaces; while hydrophobicity is more relevant for aggregation in water. A zwitterionic (POPC: 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) and an anionic lipid (POPS: 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-L-serine) are used as model lipids for WEPMEM. The addition of head group dipolar interactions in lipids significantly improved structural, dynamic and dielectric properties of the model bilayer. Using WEPMEM and WEPPROM, we studied membrane-induced peptide folding of a cationic antimicrobial peptide with anticancer activity, SVS-1. We found that membrane-induced peptide folding is driven by both (a) cooperativity in peptide self interaction and (b) cooperativity in membrane-peptide interactions. The dipolar interactions between the peptide and the lipid head-groups contribute to stabilizing folded conformations. The role of monovalent ion size and peptide concentration in driving lipid domain formation in anionic/zwitterionic lipid mixtures was also investigated. Our study suggest monovalent ion size to be a crucial determinant of interaction with lipid head groups, and hence domain formation in lipid mixtures. This study reinforces the role of dipole interactions in protein folding, lipid membrane properties, membrane induced peptide folding and lipid domain formation. Therefore, the models developed in this thesis can be used to explore a multitude of biomolecular processes, both at longer time-scales and larger system sizes.

Heat dissipation from carbon nano-electronics

The incorporation of graphitic compounds such as carbon nanotubes (CNTs) and graphene into nano-electronic device packaging holds much promise for waste heat management given their high thermal conductivities. However, as these graphitic materials must be used in together with other semiconductor/insulator materials, it is not known how thermal transport is affected by the interaction. Using different simulation techniques, in this thesis, we evaluate the thermal transport properties - thermal boundary conductance (TBC) and thermal conductivity - of CNTs and single-layer graphene in contact with an amorphous SiO2 (a-SiO2) substrate. First, the theoretical methodologies and concepts used in our simulations are presented. In particular, two concepts are described in detail as they are necessary for the understanding of the subsequent chapters. The first is the linear response Green-Kubo (GK) theory of thermal boundary conductance (TBC), which we develop in this thesis, and the second is the spectral energy density method, which we use to directly compute the phonon lifetimes and thermal transport coefficients. After we set the conceptual foundations, the TBC of the CNT-SiO2 interface is computed using non- equilibrium molecular dynamics (MD) simulations and the new Green-Kubo method that we have developed. Its dependence on temperature, the strength of the interaction with the substrate, and tube diameter are evaluated. To gain further insight into the phonon dynamics in supported CNTs, the scattering rates are computed using the spectral energy density (SED) method. With this method, we are able to distinguish the different scattering mechanisms (boundary and CNT-substrate phonon-phonon) and rates. The phonon lifetimes in supported CNTs are found to be reduced by contact with the substrate and we use that lifetime reduction to determine the change in CNT thermal conductivity. Next, we examine thermal transport in graphene supported on SiO2. The phonon contribution to the TBC of the graphene-SiO2 interface is computed from MD simulations and found to agree well with experimentally measured values. We derive the theory of remote phonon scattering of graphene electrons and compute the heat transfer coefficient dependence on doping level and temperature. The thermal boundary conductance from remote phonon scattering is found to be an order of magnitude smaller than that of the phonon contribution. The in-plane thermal conductivity of supported graphene is calculated from MD simulations. The experimentally measured order of magnitude reduction in thermal conductivity is reproduced in our simulations. We show that this reduction is due to the damping of the flexural (ZA) modes. By varying the interaction between graphene and the substrate, the ZA modes hybridize with the substrate Rayleigh modes and the dispersion of the hybridized modes is found to linearize in the strong coupling limit, leading to an increased thermal conductance in the composite structure.