Non-empirical Force-Field Development for Weakly-Bound Organic Molecules

This thesis pioneers the development of non-empirical anisotropic atom-atom force-fields for organic molecules, and their use as state-of-the-art intermolecular potentials for modelling the solid-state. The long-range electrostatic, polarization and dispersion terms have been derived directly from the molecular charge density, while the short-range terms are obtained through fitting to the symmetry-adapted perturbation theory (SAPT(DFT)) intermolecular interaction energies of a large number of different dimer configurations. This study aims to establish how far this approach, previously used for small molecules, could be applied to specialty molecules, and whether these potentials improve on the current empirical force-fields FIT and WILLIAMS01. The scaling of the underlying electronic structure calculations with system size means many adaptions have been made. This project aims to generate force-fields suitable for use in Crystal Structure Prediction (CSP) and for modelling possible polymorphs, particularly high-pressure polymorphs. By accurately modelling the repulsive wall of the potential energy surface, the high pressure/temperature conditions typically sampled by explosive materials could be studied reliably, as shown in a CSP study of pyridine using a non-empirical potential. This thesis also investigates the transferability of these potentials from the gas to condensed-phase, as well as the transferability and importance of the intermolecular interactions of flexible functional groups, in particular NO2 groups. The charge distribution was found to be strongly influenced by variations in the observed NO2 torsion angle and the conformation of the rest of the molecule. This conformation dependence coupled with the novelty of the methods and size of the molecules has made developing non-empirical models for flexible nitro-energetic materials very challenging. The thesis culminates in the development of a bespoke non-empirical force-field for rigid trinitrobenzene and its use in a CSP study

Molecular aggregation of thiols and alcohols: study of non-covalent interactions by microwave spectroscopy

El estudio y comprensión de las interacciones no covalentes a nivel molecular es un campo que está en continuo desarrollo y cobra vital importancia para determinar el comportamiento estructural de muchas moléculas de interés químico, tecnológico o biológico. En esta tésis doctoral se han analizado las interacciones intermoleculares implicadas en la formación de agregados moleculares neutros, tanto dímeros como productos de microsolvatación, en fase gas. Los complejos intermoleculares se han generado mediante expansiones supersónicas pulsadas, caracterizándose posteriormente mediante espectroscopía de rotación. Este trabajo ha utilizado dos técnicas espectroscópicas, incluyendo un espectrómetro de microondas con transformada de Fourier (FTMW) de tipo Balle-Flygare en el rango de frecuencias 8-20 GHz, y un espectrómetro de transformada de Fourier de banda ancha con excitación multifrecuencia (CP-FTMW) cubriendo el rango espectral de 2-8 GHz. Los complejos intermoleculares estudiados han incluido moléculas con grupos alcohol y/o tiol, con objeto de analizar las diferencias entre las interacciones intermoleculares que implican átomos de oxígeno o azufre, en especial el enlace de hidrógeno. Se han estudiado moléculas incluyendo tanto sistemas cíclicos alifáticos (ciclohexanol, ciclohexanotiol) como aromáticos (furfuril alcohol, furfuril mercaptano, tienil alcohol, tienil mercaptano). Los enlaces de hidrógeno analizados han comprendido especialmente interacciones de tipo O-H···O, O-H···S y S-H···S. La formación de los complejos intermoleculares ha revelado en algunos de ellos una gran variedad conformacional, como la observación de seis isómeros del dímero de ciclohexanol. En el caso de los monohidratos se han observado en algunos casos desdoblamientos asociados a movimientos internos de gran amplitud, como la rotación de la molécula de agua en los monohidratos de ciclohexanol y tienil mercaptano. En los casos de moléculas quirales la dimerización ha permitido observar la estabilidad relativa de los diastereoisómeros homo o heteroquirales. El estudio experimental se ha completado con diferentes cálculos teóricos de orbitales moleculares, en especial teoría del funcional de la densidad, a fin de caracterizar las interacciones estructuralmente, energéticamente y mediante análisis topológico de la densidad electrónica. El conjunto de datos experimentales y teóricos permite aumentar la información existente sobre enlaces de hidrógeno con átomos de azufre, generalmente poco estudiados, y su comparación con los análogos oxigenados.The study and understanding of non-covalent interactions at molecular level is a field in continuous development and essential to determine the structural behavior of many molecules of chemical, technological or biological interest. In this PhD thesis, the intermolecular interactions involved in the formation of neutral molecular aggregates, both dimers and microsolvation products, have been analyzed in the gas phase. The intermolecular complexes were generated by pulsed supersonic expansions, and later characterized by rotational spectroscopy. This work has used two spectroscopic techniques, including a Balle-Flygare Fourier-Transform Microwave (FTMW) spectrometer in the 8-20 GHz frequency range, and a broadband Chirped-Pulse Fourier Transform Microwave (CP-FTMW) spectrometer covering the 2-8GHz spectral range. The intermolecular complexes studied have included molecules with alcohol and / or thiol groups, in order to analyze the differences between the intermolecular interactions involving oxygen or sulfur atoms, especially hydrogen bonds. Molecules that comprise both aliphatic (cyclohexanol) and aromatic (furfuryl alcohol, furfuryl mercaptan, thenyl alcohol, thenyl mercaptan) ring systems have been studied. The analyzed hydrogen bonds included especially O-H···O, O-H···S and S-H···S interactions. The formation of intermolecular complexes has revealed a great conformational diversity in some of them, such as the observation of six isomers of the cyclohexanol dimer. With regard to the monohydrates, tunnelling splittings associated with internal large amplitude motions have been observed in some cases, such as the rotation of the water molecule in the monohydrates of cyclohexanol, thenyl alcohol and thenyl mercaptan. In the case of chiral molecules, dimerization has made it possible to observe the relative stability of homo- or heterochiral diastereoisomers. The experimental study has been supported by different theoretical molecular orbital calculations, in particular Density Functional Theory (DFT) calculations, in order to characterize the interactions structurally, energetically and by a topological analysis of electron density. The set of experimental and theoretical data will advance the existing information on hydrogen bonds involving sulfur atoms, generally scarcely studied, and their comparison with the oxygenated analogues.Departamento de Química Física y Química InorgánicaDoctorado en Físic

The development of hybrid quantum classical computational methods for carbohydrate and hypervalent phosphoric systems

Includes bibliographical references.Ab initio, density functional theory, and semi-empirical methods serve as major computational tools for quantum mechanical calculations of medium to large molecular systems. Semi-empirical methods are most effectively used in a hybrid quantum mechanics/molecular mechanics (QM/MM) dynamics framework. However, semi-empirical methods have been designed to provide accurate results for organic molecules, but often fail to treat hypervalent species accurately due to their use of an sp basis. Recently, significant breakthroughs have been made with the incorporation of d-orbitals into the semi-empirical framework, thereby allowing for accurate modeling of both hypervalent and transition metal systems. Here I consider two methods that adopt this new methodology, namely AM1/d-PhoT and AM1*. Our major focus is the simulation of chemical biological and more specifically chemical glycobiological problems of biochemical interest. When I tested the ability of both AM1/d-PhoT and AM1* to reproduce key metrics in chemical glycobiology (i.e., sugar ring pucker, phosphate participation in transferase reactions) these methods, in combination with the published parameters, performed very poorly. Using the AM1/d-PhoT and AM1* Hamiltonians I set out to re-parameterize these methods aiming to produce holistic biochemical QM/MM toolsets able to simulate fundamental problems of binding and enzyme reactivity in chemical glycobiology. We called these methods AM1/d-CB1 and AM1*-CB1. In the development of these parameter sets I focused specifically on proton transfer, carbohydrate ring puckering, bond polarization, amino acid interactions, and phosphate interactions (facets important to chemical glycobiology). Both AM1/d-CB1 and AM1*-CB1 make use of a variable property optimization parameter approach for the glycan molecular class and its chemical environment. The accuracy of these methods is evaluated for carbohydrates, amino acids and phosphates present in catalytic domains of glycoenzymes, and the are shown to be more accurate for key performance indices (puckering, etc.) and on average across all simulation derived properties (QM/MM polarization, protein performance, etc.) than all other NDDO semiempirical methods currently being used. A major objective of the newly developed AM1/d-CB1 and AM1*-CB1 is to provide a platform to accurately model reactions central to chemical glycobiology using hybrid QM/MM molecular dynamics (MD) simulations. AM1/d-CB1 is applied to a well-known reaction involving purine nucleoside phosphorylase (PNP) and results lead me to conclude that the method shows promise for modelling glycobiological QM/MM systems

Development and Application of Efficient Methods for the Computation of Electronic Spectra of Large Systems

In this thesis, an efficient procedure to compute electronic excitation spectra of molecular systems is presented, focusing particularly on the computation of electronic circular dichroism (ECD) spectra. ECD spectroscopy is commonly used to distinguish between the two enantiomers of a chiral compound. Due to a strong sensitivity to the three-dimensional structure, reliable simulation of ECD spectra of solvated molecules by quantum chemical methods requires the knowledge of the relevant conformers along with the corresponding ECD signals (i.e., the individual transition intensities and energies) and Boltzmann populations. The latter point can be addressed by an established thermochemical protocol. It combines electronic energies computed in gas phase by dispersion-corrected density functional theory (DFT-D) with nuclear ro-vibrational and solvation contributions to yield the free energies in solution. This model is applied to study the association of two intermolecular frustrated Lewis pairs (FLPs). Though this case study does not aim at computing an ECD spectrum, it provides insight on whether such a scheme could also be suited to rank conformers in solution. Comparison to high-level reference methods and partially available experimental data suggests that the largest uncertainty can be attributed to the implicit solvation model. The errors for different dimer arrangements, however, appear to be within the order of 1 kcal mol-1, which is encouraging for the pursued computation of conformer free energies. In combination with a quadruple-ζ basis set, hybrid DFT-D methods like the PW6B95-D3 are almost converged with respect to a complete basis and provide satisfactory results for the electronic energy contribution. Hence, they are recommended choices for the final electronic structure level to rank different conformers in routine calculations. The major part of this thesis deals with the development and application of cost-efficient excited state methods. The current state-of-the-art to compute ECD spectra for systems with roughly 100 atoms is the time-dependent density functional theory (TD-DFT) approach. Based on the latter, the simplified TD-DFT (sTD-DFT) method is developed. The excited state treatment is accelerated by at least three orders of magnitude, resulting from semiempirically approximated two-electron integrals and a significant reduction of the involved matrix dimensions. The introduced approximations are in line with the ones in the previously presented simplified Tamm-Dancoff approximated TD-DFT (sTDA-DFT). It is shown that the sTD-DFT and the sTDA-DFT approaches provide roughly the same accuracy for vertical excitation energies, as well as absorption and ECD spectra, as their parental schemes, i.e., TD-DFT and Tamm-Dancoff approximated TD-DFT (TDA-DFT), respectively. Thus, sTD-DFT is an efficient approach that is suitable for the computation of ECD spectra. Furthermore, sTD-DFT calculations conducted on "snapshots" from molecular dynamics (MD) simulations offer an appealing way to effectively incorporate vibronic effects without a quantum mechanical (QM) treatment of the nuclei. Such a treatment is exemplified for [16]helicene (102 atoms) and a di-substituted derivative (164 atoms). While the feasibility of applying sTDA-DFT to very large systems is demonstrated for two palladium(II) metallosupramolecular spheres (822 and 1644 atoms, respectively), it is also shown that this method produces ECD spectra of incorrect sign in the origin-independent dipole velocity formalism for extended π-systems. This behavior is due to the Tamm-Dancoff approximation (TDA) and, therefore, it is also present in TDA-DFT and the related configuration interaction singles (CIS) approach. Based on the insights obtained from this study, the A+B/2 correction is developed, which corrects the (simplified) TDA eigenvectors affording origin-independent dipole velocity ECD spectra of roughly (s)TD-DFT quality, while retaining the lower computational cost of the (s)TDA excited state treatment. Combination with a newly developed, purpose-specific extended tight-binding procedure for the ground state yields the ultra-fast sTDA-xTB approach. Due to different adjustments of the atomic orbital basis and the tight-binding Hamiltonian, the method is on a par with TDA-PBE0/def2-SV(P) for vertical excitation energies. The entire computation of an ECD spectrum ( The last part of this thesis reports on another purpose-specific extended tight-binding scheme, GFN-xTB, which provides molecular geometries, harmonic vibrational frequencies, and non-covalent interaction energies with comparable or better accuracy than existing semiempirical methods. Since parameters are available for all elements with Z ≤ 86, the method offers great potential to sample the conformational space of almost arbitrary molecules with up to a few hundred atoms. In combination with the ultra-fast sTDA-xTB approach, ECD spectra can be computed in an almost "black box" manner, e.g., by computing spectra on MD snapshots. Together with the established thermochemistry protocol mentioned above, the newly developed architecture sets the stage for a fully automatic multi-level ECD procedure to be developed in the near future.Diese Dissertation stellt einen effizienten Ansatz zur Berechnung von elektronischen Anregungsspektren molekularer Systeme vor, wobei der besondere Fokus auf der Berechnung von elektronischen Circulardichroismus-(ECD-)Spektren liegt. Die ECD-Spektroskopie wird typischerweise verwendet, um zwischen den beiden Enantiomeren einer chiralen Verbindung zu unterscheiden. Aufgrund der hohen Sensibilität für die räumliche Struktur des Moleküls wird zur zuverlässigen Simulation von ECD-Spektren die Kenntnis der relevanten Konformere inklusive ihrer Boltzmann-Populationen und der jeweiligen ECD-Signale (d.h. deren energetische Lage und Intensitäten) benötigt. Die Populationen können mithilfe eines literaturbekannten Thermochemieprotokolls unter Verwendung der dispersionskorrigierten Dichtefunktionaltheorie (DFT-D) näherungsweise berechnet werden. In der vorliegenden Arbeit wird dieses Modell verwendet, um die Komplexbildung von zwei intermolekularen frustrierten Lewispaaren (FLPs) zu untersuchen. Obwohl diese Fallstudie keine Berechnung eines ECD-Spektrums zum Ziel hat, geben die gewonnenen Erkenntnisse durchaus Aufschluss darüber, ob sich der gewählte Ansatz auch dazu eignet, die Populationen verschiedener Konformere zu bestimmen. Der Vergleich mit hochwertigen Vergleichsrechnungen auf der einen und mit zum Teil verfügbaren experimentellen Daten auf der anderen Seite legt nahe, dass der größte Unsicherheitsfaktor in den Solvatationsbeiträgen vorliegt, welche mithilfe eines impliziten Lösungsmittelmodells bestimmt werden. Allerdings liegen deren geschätzte Fehler für unterschiedliche räumliche Anordnungen des Komplexes, d.h. bei einer gleichbleibenden Systemgröße von ca. 50-100 Atomen, lediglich bei etwa 1 kcal mol-1. Für die Berechnung von freien konformellen Enthalpien ist mit ähnlich großen Fehlern zu rechnen. Kombiniert mit Quadruple-ζ-Basissätzen weisen Hybrid-DFT-Methoden bereits nahezu konvergierte elektronische Energien auf und können bei gleichzeitiger Verwendung einer Dispersionskorrektur relativ genaue Gasphasenenergiebeiträge (so z.B. PW6B95-D3) zu den freien Enthalpien in Lösung beitragen. Der Großteil dieser Dissertation beschäftigt sich mit der Entwicklung und Anwendung von kosteneffizienten Methoden zur Berechnung angeregter Zustände. Die gegenwärtig am häufigsten verwendete Methode zur Berechnung von ECD-Spektren ist die zeitabhängige Dichtefunktionaltheorie (TD-DFT). Von dieser ausgehend wird die vereinfachte TD-DFT Methode (sTD-DFT) entwickelt. Aufgrund der semiempirischen Näherung der Zweielektronenintegrale und der deutlichen Reduzierung der relevanten Matrixdimensionen wird die Berechnung der angeregten Zustände um mindestens drei Größenordnungen beschleunigt. Diese Näherungen sind konsistent zu jenen, die bereits in dem vereinfachten Tamm-Dancoff-genäherten TD-DFT (sTDA-DFT) Ansatz eigeführt wurden. Im Vergleich zu den Ausgangsmethoden, also TD-DFT und seiner Tamm-Dancoff-Näherung (TDA-DFT), ist weder eine signifikante Beeinträchtigung der senkrechten Anregungsenergien noch eine Verschlechterung der Absorptions- und ECD-Intensitäten bemerkbar. Insbesondere die sTD-DFT Methode eignet sich zur effizienten und zuverlässigen Berechnung von ECD-Spektren. Die Effizienz der sTD-DFT Methode ermöglicht unter anderem die Berechnung von Spektren auf Nichtminimumsstrukturen, die aus einer Molekulardynamik-(MD)-Simulation stammen. Somit können vibronische Effekte näherungsweise erfasst werden, ohne dass ein quantenmechanischer (QM) Ansatz für die Kerne verwendet werden muss. Exemplarisch wird dieses Verfahren für das [16]Helicen (102 Atome) und einem disubstituierten Derivat (164 Atome) angewandt. Die Anwendbarkeit der sTDA-DFT Methode auf sehr große Systeme wird am Beispiel von zwei Palladium(II)-metallosupramolekularen Komplexen (822 und 1644 Atome) verdeutlicht, doch zeigt eine weitere Studie, dass Tamm-Dancoff-genäherte (TDA) Methoden für die ECD Spektren von ausgedehnten, delokalisierten π-Systemen im Impulsformalismus das falsche Vorzeichen liefern. Gleiches gilt für den verwandten Konfigurationswechselwirkungs-Ansatz mit Einfachanregungen (CIS). Basierend auf den Erkenntnissen dieser Studie ist es gelungen, die sogenannte A+B/2-Näherung zu entwickeln, welche die entsprechenden Fehler in den TDA Eigenvektoren behebt, ohne die Kosten der Methode sichtlich zu erhöhen. Durch die Kombination des so korrigierten vereinfachten TDA-Ansatzes mit einer speziell optimierten semiempirischen Tight-Binding-Methode für den Grundzustand wird die äußerst schnelle sTDA-xTB-Methode erhalten. Aufgrund verschiedener Modifikationen der Atomorbitalbasis und des Tight-Binding-Potentials erreicht diese Methode eine ähnliche Genauigkeit für senkrechte Anregungsenergien wie z.B. eine DFT-basierende Rechnung auf TDA-PBE0/def2-SV(P) Niveau. Die beachtliche Effizienz der Methode wird im Vergleich zum bereits effizienten sTD-BHLYP/def2-SV(P) Ansatz für das [16]Helicen (alle Anregungen bis 9 eV) deutlich: Während letzterer Ansatz etwas mehr als eine Stunde Rechenzeit benötigt, ist das ECD-Spektrum mit sTDA-xTB bereits nach 10 s verfügbar. Da die Parametrisierung nahezu das gesamte Periodensystem abdeckt, werden Standardrechnungen von Spektren großer Systeme (mit ca. 1000 Atomen) ermöglicht, selbst wenn mehrere Konformere berücksichtigt werden. Im letzten Teil der Arbeit wird eine weitere spezialisierte Tight-Binding-Methode vorgestellt (GFN-xTB), die wiederum auf die Berechnung von Geometrien, harmonischen Frequenzen und nichtkovalenten Wechselwirkungen ausgelegt ist und hierfür bessere Ergebnisse liefert als vergleichbare semiempirische Methoden. Die Verfügbarkeit von Parametern für alle Elemente mit Z ≤ 86 ermöglicht das Absuchen des konformellen Raums für unterschiedliche Systeme mit wenigen hundert Atomen. Zusammen mit sTDA-xTB sind in kürzester Zeit Berechnungen von Sprektren z.B. entlang von MD-Trajektorien möglich. Vereint mit den bereits existierenden Thermochemieprotokollen sind somit die ersten Voraussetzungen für eine völlig automatische Prozedur zur Berechnung von ECD-Spektren geschaffen worden

Classical And Quantum Mechanical Simulations Of Condensed Systems And Biomolecules

This work describes the fundamental study of two enzymes of Fe(II)/-KG super family enzymes (TET2 and AlkB) by applying MD and QM/MM approaches, as well as the development of multipolar-polarizable force field (AMOEBA/GEM-DM) for condensed systems (ionic liquids and water). TET2 catalytic activity has been studied extensively to identify the potential source of its substrate preference in three iterative oxidation steps. Our MD results along with some experimental data show that the wild type TET2 active site is shaped to enable higher order oxidation. We showed that the scaffold stablished by Y1902 and T1372 is required for iterative oxidation. The mutation of these residues perturbs the alignment of the substrate in the active site, resulting in “5hmC-stalling” phenotype in some of the mutants. We provided more details on 5hmC to 5fC oxidation mechanism for wild type and one of the “5hmC-stallling” mutants (E mutant). We showed that 5hmC oxidizes to 5fC in the wild type via three steps. The first step is the hydrogen atom abstraction from hydroxyl group of 5hmC, while the second hydrogen is transferred from methylene group of 5hmC through the third transition state as a proton. Our results suggest that the oxidation in E mutant is kinetically unfavorable due to its high barrier energy. Many analyses have been performed to qualitatively describe our results and we believed our results can be used as a guide for other researchers. In addition, two MD approaches (explicit ligand sampling and WHAM) are used to study the oxygen molecule diffusion into the active site of AlkB. Our results showed that there are two possible channels for oxygen diffusion, however, diffusion through one of them is thermodynamically favorable. We also applied multipolar-polarizable force field to describe the oxygen diffusion along the preferred tunnel. We showed that the polarizable force field can describe the behavior of the highly polarizable systems accurately. We also developed a new multipolar-polarizable force field (AMOEBA/GEM-DM) to calculate the properties of imidazolium- and pyrrolidinium- based ionic liquids and water in a range of temperature. Our results agree well with the experimental data. The good agreement between our results and experimental data is because our new parameters provide an accurate description of non-bonded interactions. We fit all the non-bonded parameters against QM. We use the multipoles extracted from fitted electron densities (GEM) and we consider both inter- and intra-molecular polarization. We believe this method can accurately calculate the properties of condensed systems and can be helpful for designing new systems such as electrolytes

Pharmacophore derivation using discotech and comparison of semi-emperical, AB initio and density functional CoMFA studies for sigma 1 and sigma 2 receptor-ligands

This study describes the development of pharmacophore and CoMFA models for sigma receptor ligands. CoMFA studies were performed for 48 bioactive sigma 1 receptorligands using [H3 ](+) pentazocine as the radioligand, for 30 PCP derivatives for sigma 1 receptor-ligands using [3H](+)SK-F 10047 as the radioligand and for 24 bioactive sigma 2 receptor-ligands using the radioligand [H3](+)DTG in the presence of pentazocine. Distance Comparisons (DISCOtech) was used as the starting point for CoMFA studies. The conformers, derived by DISCOtech were optimized using AMi, or HF/3-21G* in Gaussian 98. The optimized geometries were aligned with the pharmacophore, derived using DISCOtech. Atomic charges were calculated using AMl, HF/3-21G*, B3LYP/3-21G*, MP2/3-21G* methods in Gaussian 98. The CoMFA Maps that were developed using Sybyl 6.9 were compared on steric and electrostatic field differences. With leaveone-out cross validation the numbers of optimal components were decided. Using these numbers of optimal components no cross validation was performed in a training set. After a test set, it was known that CoMFA models derived from HF/3-21G* optimized geometries were more reliable in predicting bioactivities than CoMFA models derived from AMi optimized geometries

Computational studies of protein-ligand recognition

Molecular recognition between biomolecules and ligands is very specific in living cells. The functions of all biochemical processes and cell mechanisms are dependent upon complex but specific non-covalent intermolecular interactions. As essential building blocks in protein and nucleic acid, phosphate groups are commonly found in nucleic acids, proteins, and lipids. Nearly half of known proteins have been shown to interact with ligands containing a phosphate group. Binding of a phosphoryl group is fundamental to a range of biological processes including metabolism, biosynthesis, gene regulation, signal transduction, muscle contraction, and antibiotic resistance. Phosphorylation is one of the most common forms of reversible posttranslational modification of protein and, nearly 30% of all proteins are phosphorylated on at least one residue in cells. However, phosphate binding sites are less well defined and fundamental principles of why and how proteins recognize phosphate groups are not yet fully understood. Molecular modeling is a common tool for studying biomolecular structure, dynamics, interaction and function. Due to the complex electrostatics, high concentration of ions and intricate interactions with environment, however, the modeling and designing of highly charged drug-like molecules and nucleic acid derivatives are extremely difficult. This thesis will focus on the highly charged phosphate, including its different protonation states, and energetic and thermodynamic driving forces behind protein-phosphate recognition. This thesis work will also discuss the development of more sophisticated computational models, AMOEBA+, that are necessary for a better understanding and prediction of the physical properties of small organic molecules. Four projects will be discussed in this dissertation: two projects on force field development, and two on applying molecular dynamic simulations to understand biological processes. These projects have led to new insights into understanding of physical and chemical principles and mechanisms underlying highly protein-phosphate binding and nucleic acid stability. In addition, this thesis work will enhance the capability to develop and apply computational and theoretical frameworks to model, predict and design proteins, therapeutics, and diagnostic strategies targeting phosphates, phosphate-containing biomoleculesBiomedical Engineerin

Binding of chlorinated environmentally active chemicals to soil surfaces: Chromatographic measurements and quantum chemicalSimulations

Adsorption studies of hexachlorobenzene (HCB) on the different well-characterized soil samples were performed. A new soil organic matter (SOM) model has been developed. Interaction of this model with HCB has been studied using different quantum-mechanical methods and molecular dynamics simulations. It has been explored that the alkylated aromatic, phenol, and lignin monomer compounds dominate the adsorption process. Moreover it was found that the most vital physical properties controlling this interaction are polarizability, molar volume, and charges of C atoms of the soil constituents