Spectroscopic properties from hybrid QM, MM molecular dynamics simulation

The central aim of this thesis work is the application and further development of a hybrid quantum mechanical/molecular mechanics (QM/MM) based approach to compute spectroscopic properties of molecules in complex chemical environments from electronic structure theory. In the framework of this thesis, an existing density functional theory implementation of the QM/MM approach is first used to calculate the nuclear magnetic resonance (NMR) solvent shifts of an adenine molecule in aqueous solution. The findings show that the aqueous solvation with its strongly fluctuating hydrogen bond network leads to specific changes in the NMR resonance lines. Besides the absolute values, also the ordering of the NMR lines changes under the influence of the solvating water molecules. Without the QM/MM scheme, a quantum chemical calculation could have led to an incorrect assignment of these lines. The second part of this thesis describes a methodological improvement of the QM/MM method that is designed for cases in which a covalent chemical bond crosses the QM/MM boundary. The development consists in an automatized protocol to optimize a so-called capping potential that saturates the electronic subsystem in the QM region. The optimization scheme is capable of tuning the parameters in such a way that the deviations of the electronic orbitals between the regular and the truncated (and "capped") molecule are minimized. This in turn results in a considerable improvement of the structural and spectroscopic parameters when computed with the new optimized capping potential within the QM/MM technique. This optimization scheme is applied and benchmarked on the example of truncated carbon-carbon bonds in a set of small test molecules. It turns out that the optimized capping potentials yield an excellent agreement of NMR chemical shifts and protonation energies with respect to the corresponding full molecules. These results are very promising, so that the application to larger biological complexes will significantly improve the reliability of the prediction of the related spectroscopic properties.

A novel computer simulation method for simulating the multiscale transduction dynamics of signal proteins

Signal proteins are able to adapt their response to a change in the environment, governing in this way a broad variety of important cellular processes in living systems. While conventional molecular-dynamics (MD) techniques can be used to explore the early signaling pathway of these protein systems at atomistic resolution, the high computational costs limit their usefulness for the elucidation of the multiscale transduction dynamics of most signaling processes, occurring on experimental timescales. To cope with the problem, we present in this paper a novel multiscale-modeling method, based on a combination of the kinetic Monte-Carlo- and MD-technique, and demonstrate its suitability for investigating the signaling behavior of the photoswitch light-oxygen-voltage-2-Jα domain from Avena Sativa (AsLOV2-Jα) and an AsLOV2-Jα-regulated photoactivable Rac1-GTPase (PA-Rac1), recently employed to control the motility of cancer cells through light stimulus. More specifically, we show that their signaling pathways begin with a residual re-arrangement and subsequent H-bond formation of amino acids near to the flavin-mononucleotide chromophore, causing a coupling between β-strands and subsequent detachment of a peripheral α-helix from the AsLOV2-domain. In the case of the PA-Rac1 system we find that this latter process induces the release of the AsLOV2-inhibitor from the switchII-activation site of the GTPase, enabling signal activation through effector-protein binding. These applications demonstrate that our approach reliably reproduces the signaling pathways of complex signal proteins, ranging from nanoseconds up to seconds at affordable computational costs.

Monte Carlo simulation of a dynamic MLC: implementation and applications

PURPOSE: Study of behavior and influence of a multileaf collimator (MLC) on dose calculation, verification, and portal energy spectra in the case of intensity-modulated fields obtained with a step-and-shoot or a dynamic technique. METHODS: The 80-leaf MLC for the Varian Clinac 2300 C/D was implemented in a previously developed Monte Carlo (MC) based multiple source model (MSM) for a 6 MV photon beam. Using this model and the MC program GEANT, dose distributions, energy fluence maps and energy spectra at different portal planes were calculated for three different MLC applications. RESULTS: The comparison of MC-calculated dose distributions in the phantom and portal plane, with those measured with films showed an agreement within 3% and 1.5 mm for all cases studied. The deviations mainly occur in the extremes of the intensity modulation. The MC method allows to investigate, among other aspects, dose components, energy fluence maps, tongue-and-groove effects and energy spectra at portal planes. CONCLUSION: The MSM together with the implementation of the MLC is appropriate for a number of investigations in intensity-modulated radiation therapy (IMRT).

Range of motion after computed tomography-based simulation of intertrochanteric corrective osteotomy in cases of slipped capital femoral epiphysis: comparison of uniplanar flexion osteotomy and multiplanar flexion, valgisation, and rotational osteotomies

BACKGROUND: Various osteotomy techniques have been developed to correct the deformity caused by slipped capital femoral epiphysis (SCFE) and compared by their clinical outcomes. The aim of the presented study was to compare an intertrochanteric uniplanar flexion osteotomy with a multiplanar osteotomy by their ability to improve postoperative range of motion as measured by simulation of computed tomographic data in patients with SCFE. METHODS: We examined 19 patients with moderate or severe SCFE as classified based on slippage angle. A computer program for the simulation of movement and osteotomy developed in our laboratory was used for study execution. According to a 3-dimensional reconstruction of the computed tomographic data, the physiological range was determined by flexion, abduction, and internal rotation. The multiplanar osteotomy was compared with the uniplanar flexion osteotomy. Both intertrochanteric osteotomy techniques were simulated, and the improvements of the movement range were assessed and compared. RESULTS: The mean slipping and thus correction angles measured were 25 degrees (range, 8-46 degrees) inferior and 54 degrees (range, 32-78 degrees) posterior. After the simulation of multiplanar osteotomy, the virtually measured ranges of motion as determined by bone-to-bone contact were 61 degrees for flexion, 57 degrees for abduction, and 66 degrees for internal rotation. The simulation of the uniplanar flexion osteotomy achieved a flexion of 63 degrees, an abduction of 36 degrees, and an internal rotation of 54 degrees. CONCLUSIONS: Apart from abduction, the improvement in the range of motion by a uniplanar flexion osteotomy is comparable with that of the multiplanar osteotomy. However, the improvement in flexion for the simulation of both techniques is not satisfactory with regard to the requirements of normal everyday life, in contrast to abduction and internal rotation. LEVEL OF EVIDENCE: Level III, Retrospective comparative study.

Are Today’s Medical School Graduates Performing the Same Number of Medical Procedures Compared to Graduates Ten Years Ago? A case for Simulation?

INTRODUCTION: Medical schools are charged with providing both a strong basic science and clinical curriculum for their students. In most institutions instruction in performing the core clinical procedures is part of the curriculum, but because of many constraints do medical students practice these procedures as many times as medical students in the past? Several studies have concluded that medical students today feel incompetent to perform basic clinical procedures at the time of graduation. [See PDF for complete abstract]

Construct Validity of the Pig Intestine Model in the Simulation of Laparoscopic Urethrovesical Anastomosis

Introduction: Laparoscopic training models are increasingly important in urology to allow trainees to improve their laparoscopic skills prior to going to the operating room. For a training model to be valid, it must correlate with performance in a real case. The model must also discriminate between experienced and inexperienced subjects. [See PDF for complete abstract]

Simulación atomística de metales líquidos y aleaciones para reactores de fusión nuclear = Atomistic simulation of liquid metals and alloys for nuclear fusion reactors

La presente tesis comprende un estudio de metales líquidos, Li, Pb y eutéctico Li17Pb en el ámbito de la tecnología de fusión nuclear. Uno de los problemas fundamentales en futuros reactores de fusión es la producción y extracción de tritio en la denominada envoltura regeneradora (blanket en inglés). Dicho blanket tendrá dos propósitos, la extracción del calor generado por las reacciones de fusión para su posterior conversión en energía eléctrica así como la producción de tritio para realimentar el proceso. Dicha producción se realizará mediante el “splitting” del Li con los neutrones provenientes de la fusión. Esta reacción produce tritio y helio por lo que la interacción del T y el He con el metal líquido, con los materiales estructurales así como con el He es un problema fundamental aun no bien entendido y de gran importancia para futuros diseños. Los capítulos 1 2 y 3 presentan una introducción a dichos problemas. El capítulo 1 introduce al lector en la tecnología de fusión nuclear. El segundo capítulo explica en mayor detalle el uso de metales líquidos en reactores de fusión, no solo en blankets sino también como primera pared, divertor etc, lo que se denomina en general “plasma facing materials”. Por último se ofrece una breve introducción a las técnicas de dinámica molecular clásica (CMD) y un breve resumen de los potenciales más usados. El estudio se ha llevado a cabo utilizando simulación atomística mediante potenciales semi-empíricos del tipo átomo embebido (EAM). La Tesis consta de 4 partes bien definidas. En primer lugar se verificó la idoneidad de los potenciales tipo EAM para simular las propiedades de los metales Li y Pb en fase líquida. Dicho estudio se detalla en el Capítulo 4 y en su extensión, el Apéndice 1, en el que se estudia los límites de validez de esta aproximación. Los resultados de dicho estudio han sido publicados y presentados en diversos congresos internacionales. Un resumen de la metodología seguida fue publicado como capítulo de libro en Technofusión 2011. Los resultados se presentaron en diversos congresos internacionales, entre ellos ICENES 2011, (Artículo en ICENES Proceedings) ICOPS-SOFE 2011, en una presentación oral etc. El trabajo ha sido aceptado recientemente en Journal of Nuclear Materiales (Fraile et al 2012). La segunda parte y más importante comprende el desarrollo de un potencial para el estudio de la mezcla de ambos metales. Éste es el trabajo más novedoso e importante dado que no existía en la literatura un potencial semejante. Se estudiaron dos aproximaciones distintas al problema, un potencial tipo EAM/cd y un potencial EAM/alloy. Ambos potenciales dan resultados satisfactorios para la simulación del eutéctico (y concentraciones de Li menores que el 17%). Sin embargo el sistema LiPb en todas las concentraciones es un sistema que se aparta enormemente de una solución ideal y dicho potencial no daba buenos resultados para mezclas PbLi con concentraciones de Li grandes. Este problema fue solventado mediante el desarrollo de un segundo potencial, esta vez tipo EAM/alloy (segunda parte del Capítulo 5). Dicho trabajo será enviado a Physical Review Letters o a Phys. Rev. B, y una extensión junto con un estudio detallado de las propiedades del eutéctico de acuerdo con nuestras simulaciones se enviará a continuación a Phys. Rev. B. En tercer lugar se estudió el problema de la difusividad del H en metales líquidos aprovechando distintos potenciales existentes en la literatura. El problema del H en metales líquidos es importante en metalurgia. En dicho capítulo se estudió la difusividad del H en Pd, Ni y Al con potenciales tipo EAM, y también con un potencial más sofisticado que tiene en cuenta la dependencia angular de las interacciones (ADP por sus siglas en inglés). De este modo disponemos de un estudio detallado del problema con diferentes modelos y diferentes metales. La conclusión apunta a que si se compara con los resultados experimentales (muy escasos) los resultados obtenidos mediante CMD dan valores bajos de la difusividad del H. Las razones de dicho desacuerdo entre simulación y experimentos se detallan en el Capítulo 6. Este trabajo ha sido presentado en una presentación oral en el reciente congreso internacional “Trends on Nanothecnology” TNT 2012 celebrado en Madrid. El trabajo será publicado en un futuro próximo. Por último, como se dijo anteriormente, el estudio del He, la formación de burbujas en metales líquidos, su difusión nucleación y cavitación es otro problema deseable de ser estudiado mediante técnicas atomísticas. Para ello es necesario el desarrollo de diversos potenciales, He-Li, He-Pb y un potencial ternario Pb-Li-He. Para ello se han realizado simulación ab initio de los sistemas Pb+He y Li+He. Dicho estudio pretende calcular las fuerzas entre los átomos del metal (Pb o Li) con intersticiales de He. De este modo aplicaremos el “force matching method” (FMM) para el desarrollo de dichos potenciales. En el Capítulo 7 se detallan los resultados obtenidos referidos a las posiciones más favorables de las impurezas de He dentro de redes cristalinas de Pb y Li así como el efecto de tener en cuenta el acoplo spin-orbita (SOC en inglés). El análisis de los resultados en términos de transferencia de carga y análisis de las densidades electrónicas, así como la creación de los potenciales mencionados está en progreso. En conjunto la tesis presenta un estudio de los diversos problemas relacionados con el uso de metales líquidos en reactores de fusión y representa un primer paso en la determinación de parámetros de gran importancia para el diseño de blankets y sistemas de primera pared. Con la simulación MD de dichos problemas mediante, importante, potenciales realistas, valores de difusión, solubilidad etc de especies ligeras, H (o sus isotopos) y He en metales líquidos podrá ser calculada complementando así la base de datos que presenta enormes incertidumbres.

Molecular dynamics modeling and simulation of void growth in two dimensions

The mechanisms of growth of a circular void by plastic deformation were studied by means of molecular dynamics in two dimensions (2D). While previous molecular dynamics (MD) simulations in three dimensions (3D) have been limited to small voids (up to ≈10 nm in radius), this strategy allows us to study the behavior of voids of up to 100 nm in radius. MD simulations showed that plastic deformation was triggered by the nucleation of dislocations at the atomic steps of the void surface in the whole range of void sizes studied. The yield stress, defined as stress necessary to nucleate stable dislocations, decreased with temperature, but the void growth rate was not very sensitive to this parameter. Simulations under uniaxial tension, uniaxial deformation and biaxial deformation showed that the void growth rate increased very rapidly with multiaxiality but it did not depend on the initial void radius. These results were compared with previous 3D MD and 2D dislocation dynamics simulations to establish a map of mechanisms and size effects for plastic void growth in crystalline solids.

Computer simulation of the effect of cargo shifting on articulated vehicles performing braking and cornering maneuvers. Volume 1: executive summary. Final report.

Federal Highway Administration, Structures and Applied Mechanics Division, Washington, D.C.

Computer simulation of the effect of cargo shifting on articulated vehicles performing braking and cornering maneuvers. Volume 2: technical report. Final report.

Federal Highway Administration, Structures and Applied Mechanics Division, Washington, D.C.

Computer simulation of the effect of cargo shifting on articulated vehicles performing braking and cornering maneuvers. Volume 4: user's manual for TDVS/SLOSH. Final report.

Federal Highway Administration, Structures and Applied Mechanics Division, Washington, D.C.

Computer simulation of the effect of cargo shifting on articulated vehicles performing braking and cornering maneuvers. Volume 3: technical supplement. Final report.

Federal Highway Administration, Structures and Applied Mechanics Division, Washington, D.C.

Computer simulation of the effect of road roughness on tire-pavement forces for an articulated vehicle performing braking and cornering maneuvers. Phase report.

Federal Highway Administration, Washington, D.C.

Development of cost simulation study of alcoholism insurance benefit packages : executive summary.

"May 1983."