Simulation studies for surfaces and materials strength

A realistic potential energy function comprising angle dependent terms was employed to describe the potential surface of the N+O2 system. The potential energy parameters were obtained from high level ab-initio results using a nonlinear fitting procedure. It was shown that the potential function is able to reproduce a large number of points on the potential surface with a small rms deviation. A literature survey was conducted to analyze exclusively the status of current small cluster research. This survey turned out to be quite useful in understanding and finding out the existing relationship between theoretical as well as experimental investigative techniques employed by different researchers. Additionally, the importance of the role played by computer simulation in small cluster research, was documented

High-Throughput Atomistic Modeling of Biomolecular Structure and Association

The reliability of many protein models arising from structure prediction methods is unclear. Here we present a method for absolute quality control of theoretical protein models, which can significantly contribute to their acceptance in the life-science research. We apply these methods to gain insight into the family of hydrophobins and modify them for increased cell adhesion to allow for the coating of implants. The novel proteins were shown to bind cells, while impeding bacterial adhesion

pH-DEPENDENT FREE ENERGY CALCULATIONS FOR EXPLICIT SOLVENT MOLECULAR DYNAMICS

Designing drugs for treating diseases is one of the main motivations for understanding how proteins are able to recognize their substrates. Recent growth in computational power has encouraged the use of numerical tools like atomic detailed molecular dynamics for investigating proteins. Until recently, atomic detail molecular dynamics did not allow for the transfer of protons in the solute or solvent of the model during dynamics. Modeling this transfer in the protein is important because there are seven titratable amino acids. This means that they can exist in different protonation states or states of charge. The most important titratable sites are usually deeply buried. Several methods are available for doing proton dynamics for the titratable amino acids of the solute. Unfortunately deeply buried sites challenge available methods because the models need to capture the hydrophobic effect of buried regions, the hydrophilic effect of solvent penetration and the subtlety of charged networks. These effects sometimes assist, compete, or balance each other. One solution for the above challenges is to exploit the accuracy that comes with a full atomic detailed explicitly solvated model. However such an approach runs into problems because protonation state changes at 300K require unreasonably long simulations due to solvent reorientation relaxation times. As a result, currently available methods compromise the atomic detail description in some way, either by using continuum protonation states, by using continuum solvent, or by stepping back from the atomic detail description. Our method uses both discrete protonation states and atomic detail explicit solvent. The water orientation problem is overcome by using elevated temperatures, and the information from a wide range of temperatures, including those at 300K, are woven together with our Weighted Histogram algorithm. This then gives us an accurate density of states, from which we can calculate a full range of thermodynamic results. We used our methods to calculate the Bond Dissociation Energy (BDE) of the H-S bond in the solvated single site Cysteine system. This calculated BDE for Cysteine = 90.3-+1 kcal/mole. We have found this number agrees to within 3% of the experimental BDE of a very similar bond in thiomethane, H-SCH3. The experimental BDE for the H-S bond in thio-methane is 88-+1 kcals/mole. This is very good agreement and is some validation of our methods

Structure, solvation, thermodynamics and fragmentation of molecular clusters

Cette thèse vise à étudier en détail le comportement d'agrégats moléculaires complexes et se concentre sur deux aspects principaux. Tout d'abord, la description des isomères de faible énergie des clusters d'ammonium et ammoniac et (H2O)1-7,11,12UH+ à travers l'exploration des surfaces d'énergie potentielle (PES) en utilisant une combinaison d'approches d'optimisation globales et locales. Les propriétés structurelles, de solvatation et thermodynamiques des isomères de basse énergie nouvellement identifiés ont été caractérisées. Par la suite, des simulations dynamiques de la dissociation induite par collision des (H2O)1-7,11,12UH+ et Py2+ ont été réalisées et analysées en termes de : mécanisme de dissociation, répartition d'énergie, spectres de masse et sections efficaces de collision pour complémenter des mesures expérimentales récentes menées sur ces espèces. L'optimisation globale des clusters (H2O)1-10NH4+ et (H2O)1-10NH3 a été réalisée au niveau de théorie SCC-DFTB (pour self-consistent-charge density-functional based tight-binding), pour laquelle des paramètres N-H améliorés ont été proposés, en combinaison avec l'approche d'exploration PTMD (pour parallel-tempering molecular dynamics). Les isomères de basse énergie nouvellement déterminés ont été optimisés au niveau MP2 afin d'évaluer la fiabilité de nos paramètres N-H modifiés. Les structures et les énergies de liaison obtenues avec la méthode SCC-DFTB sont en très bon accord avec les résultats de niveau MP2/Def2TZVP, ce qui démontre la capacité de l'approche SCC-DFTB à décrire la PES de ces espèces moléculaires et représente ainsi une première étape vers la modélisation d'agrégats complexes d'intérêt atmosphérique. L'intérêt porté aux (H2O)1-7,11,12UH+ vise à fournir une description détaillée d'expériences récentes de dissociation induite par collision (CID). Premièrement, les isomères stables des (H2O)1-7,11,12UH+ sont calculés en utilisant la même méthodologie que celle décrite ci-dessus. Ensuite, des simulations dynamiques des collisions entre isomères (H2O)1-7,11,12UH+ et un atome d'argon sont réalisées à énergie de collision constante au niveau SCC-DFTB. La proportion simulée d'agrégats neutres contenant l'uracile par rapport à celle d'agrégats chargés contenant l'uracile, la section efficace de fragmentation ainsi que les spectres de masse sont cohérents avec les données expérimentales ce qui met en évidence la précision de nos simulations. Ces dernières permettent de sonder en details les fragments qui se forment aux temps courts et de rationaliser la localisation du proton en excès sur ces fragments. Cette dernière propriété est fortement influencée par la nature de l'agrégat soumis à la collision. L'analyse de la proportion des fragments en fonction du temps et des spectres de masse démontrent que, jusqu'à 7 molécules d'eau, un mécanisme de dissociation direct alors que pour 11,12 molécules, un mécanisme statistique est plus susceptible d'intervenir. Enfin, des simulations d'expériences CID du Py2+ à différentes énergies de collision, entre 2,5 et 30 eV, sont présentées. Les simulations permettent de comprendre les processus de dissociation mis en jeu. L'accord entre les spectres de masse simulés et mesurés suggère que les principaux processus sont bien pris en compte par cette approche. Il semble que la majeure partie de la dissociation se produise sur une courte échelle de temps (moins de 3 ps). L'analyse de la répartition d'énergie cinétique est utilisée pour obtenir des informations sur les processus de collision/dissociation à l'échelle atomique. Les spectres de masse simulés des clusters parents et dissociés sont obtenus à partir en combinant simulations de dynamique moléculaire et théorie de l'espace des phases pour traiter respectivement la dissociation aux courtes et longues échelles de temps.This thesis aims at studying in details the behavior of complex molecular clusters and focuses on two main aspects. First, the description of low-energy isomers of ammonium/ammonia water clusters and (H2O)1-7,11,12UH+ through an extensive exploration of potential energy surfaces (PES) using a combination of global and local optimization schemes. Structural, solvation and thermodynamics properties of the newly identified low-energy isomers were characterized. Second, the dynamical simulations of collision-induced dissociation of (H2O)1-7,11,12UH+ and Py2+ were carried out to explore collision trajectories, dissociation mechanism, energy partition, mass spectra, and collision cross sections to complement experimental measurements conducted on these species. Global optimization of (H2O)1-10NH4+ and (H2O)1-10NH3 clusters is conducted at the self-consistent-charge density-functional based tight-binding (SCC-DFTB) level of theory, for which improved N-H parameters are proposed, in combination with the parallel-tempering molecular dynamics (PTMD) approach. Low-energy isomers of (H2O)1-10NH4+ and (H2O)1-10NH3 are further optimized at MP2 level in order to evaluate the reliability of our modified N-H parameters. Both structures and binding energies obtained at SCC-DFTB agree with the results at MP2/Def2TZVP level, which demonstrates the ability of SCC-DFTB to describe the PES of molecular species and represents a first step towards the modeling of complex aggregates of atmospheric interest. Focus on (H2O)1-7,11,12UH+ aims at providing a detailed description of recent collision-induced dissociation (CID) experiments. First, stable isomers of (H2O)1-7,11,12UH+ are calculated using the same methodology as described above. Then, dynamical simulations of the collisions between various (H2O)1-7,11,12UH+ isomers and argon is conducted at a constant collision energy at the SCC-DFTB level. Simulated proportion of formed neutral vs. protonated uracil containing clusters, fragmentation cross-section as well as mass spectra are consistent with the experimental data which highlights the accuracy of our simulations. They allow to probe which fragments are formed on the short time scale and rationalize the location of the excess proton on these fragments. This latter property is highly influenced by the nature of the aggregate undergoing the collision. Analyses of proportion of time-dependent fragments and mass spectra demonstrate that, up to 7 water molecules, a shattering mechanism occurs after collision whereas for n=11,12 a statistical mechanism is more likely to participate. Dynamical simulation of CID experiments of Py2+ for different collision energies between 2.5 and 30 eV is also presented. The dynamical simulations allow to understand the dissociation processes. The agreement between the simulated and measured mass spectra suggests that the main processes are captured by this approach. It appears that most of the dissociation occurs on a short timescale (less than 3 ps). Analysis of the kinetic energy partition is used to get insights into the collision/dissociation processes at the atomic scale. The simulated mass spectra of the parent and dissociated products are obtained from the combination of molecular dynamics simulations and phase space theory to address the short and long timescales dissociation, respectively

CHARMM: The biomolecular simulation program

CHARMM (Chemistry at HARvard Molecular Mechanics) is a highly versatile and widely used molecular simulation program. It has been developed over the last three decades with a primary focus on molecules of biological interest, including proteins, peptides, lipids, nucleic acids, carbohydrates, and small molecule ligands, as they occur in solution, crystals, and membrane environments. For the study of such systems, the program provides a large suite of computational tools that include numerous conformational and path sampling methods, free energy estimators, molecular minimization, dynamics, and analysis techniques, and model-building capabilities. The CHARMM program is applicable to problems involving a much broader class of many-particle systems. Calculations with CHARMM can be performed using a number of different energy functions and models, from mixed quantum mechanical-molecular mechanical force fields, to all-atom classical potential energy functions with explicit solvent and various boundary conditions, to implicit solvent and membrane models. The program has been ported to numerous platforms in both serial and parallel architectures. This article provides an overview of the program as it exists today with an emphasis on developments since the publication of the original CHARMM article in 1983. © 2009 Wiley Periodicals, Inc.J Comput Chem, 2009.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63074/1/21287_ftp.pd

Exciton Diffusion, Transport, and Localization in Conjugated Polymers

Conjugated polymers are wide bandgap semiconductors which have a series of conjugated π-orbitals that extend along the polymer ‘backbone’. The π-orbital conjugation can be disrupted by twisting of the polymer, affecting their optical properties. These materials are very useful for devices, where they are frequently found in semicrystalline thin films. In thin films, Frenkel excitons diffuse on a nanometer scale. However, measurement of the diffusion length of excitons in conjugated polymer films is currently very difficult. Disordered packing and twisting of polymers plays a significant role, but has not been examined in detail. This dissertation presents methods of measuring exciton diffusion length in polymer films and nanoparticles and explains the effect of nuclear disorder on the optical spectra and exciton diffusion in semicrystalline polymer films

Feet on the potential energy surface, head in the π clouds

The landscape of a potential energy surface is marked by chemically interesting features. Hills and valleys correspond to transition states and reactive intermediates; the deepest valley gives the most stable configuration. Mapping these features for individual molecules and for the interactions between molecules is one of the goals of computational chemistry. The dispersion energy is a weak attractive force in intermolecular interactions. Dispersion energy results from a purely quantum mechanical effect, in which instantaneous multipoles on one molecule induce multipoles on another. Among neutral atoms or molecules that lack permanent multipole moments, the dispersion interaction is the principal attractive force. Dispersion also plays a significant role in the interaction between molecules with diffuse π clouds. This interaction is often difficult to capture with standard computational chemistry methods, so a comparison of the results obtained with various methods is itself important. This work presents explorations of the potential energy surface of clusters of atoms and of the interactions between molecules. First, structures of small aluminum clusters are examined and classified as ground states, transition states, or higher-order saddle points. Subsequently, the focus shifts to dispersion-dominated π-π interactions when the potential energy surfaces of benzene, substituted benzene, and pyridine dimers are explored. Because DNA nucleotide bases can be thought of as substituted heterocycles, a natural extension of the substituted benzene and pyridine investigations is to model paired nucleotide bases. Finally, the success of the dispersion studies inspires the development of an extension to the computational method used, which will enable the dispersion energy to be modeled - and the potential energy surface explored - in additional chemical systems

Residue contact-count potentials are as effective as residue-residue contact-type potentials for ranking protein decoys

<p>Abstract</p> <p>Background</p> <p>For over 30 years potentials of mean force have been used to evaluate the relative energy of protein structures. The most commonly used potentials define the energy of residue-residue interactions and are derived from the empirical analysis of the known protein structures. However, single-body residue 'environment' potentials, although widely used in protein structure analysis, have not been rigorously compared to these classical two-body residue-residue interaction potentials. Here we do not try to combine the two different types of residue interaction potential, but rather to assess their independent contribution to scoring protein structures.</p> <p>Results</p> <p>A data set of nearly three thousand monomers was used to compare pairwise residue-residue 'contact-type' propensities to single-body residue 'contact-count' propensities. Using a large and standard set of protein decoys we performed an in-depth comparison of these two types of residue interaction propensities. The scores derived from the contact-type and contact-count propensities were assessed using two different performance metrics and were compared using 90 different definitions of residue-residue contact. Our findings show that both types of score perform equally well on the task of discriminating between near-native protein decoys. However, in a statistical sense, the contact-count based scores were found to carry more information than the contact-type based scores.</p> <p>Conclusion</p> <p>Our analysis has shown that the performance of either type of score is very similar on a range of different decoys. This similarity suggests a common underlying biophysical principle for both types of residue interaction propensity. However, several features of the contact-count based propensity suggests that it should be used in preference to the contact-type based propensity. Specifically, it has been shown that contact-counts can be predicted from sequence information alone. In addition, the use of a single-body term allows for efficient alignment strategies using dynamic programming, which is useful for fold recognition, for example. These facts, combined with the relative simplicity of the contact-count propensity, suggests that contact-counts should be studied in more detail in the future.</p