High performance RF/mixed signal systems require new interconnect strategies to combine high frequency (microwave/mm-wave) circuitry with silicon mixed-signal and baseband digital processing. In such systems, heterogeneous vertical integration, in which circuits in different technologies can be stacked on top of each other within the system architecture, can reduce the overall system size and power consumption. Chip stacking also enables optimally-performing heterogeneous systems, because each level of the stack can consist of components fabricated in their most suited device or substrate technology. Two novel approaches for the vertical interconnection of heterogeneous integrated systems are proposed in this work. These approaches are related to flip-chip bonding techniques used in Radio-Frequency (RF)/microwave integrated circuits. The first proposed approach involves an interlocking mechanical structure that supports flip-chip assembled Monolithic Microwave Integrated Circuits (MMICs). Photolithographically patterned thick-film SU-8 structures are applied to both the chip and the carrier such that the chip self-aligns into place and mates with the carrier. Gold bumps embedded within the structures electrically connect the chip pads to the carrier pads. This method is demonstrated through the assembly of a SiGe power amplifier MMIC onto a high resistivity silicon carrier. The second proposed approach involves vertical interconnects consisting of room temperature liquid-state metals. The fluid nature of the liquid bumps allows them to be robust in the presence of thermo-mechanical stresses, such as Coefficient of Thermal Expansion (CTE) mismatch between the interconnected chips. SU-8 structures are used to form a shaping mold on the bottom carrier that contains the liquid metal. Gold posts are electroplated on the top chip, then mated with the SU-8 mold, thereby making contact with the liquid metal to form the electrical continuity. For each of these proposed methods, design and fabrication considerations are discussed in detail. RF measurements on prototype structures up to Ka band are performed to verify the functionality of the proposed methods. Given the results of these proof-of-concept efforts, electrical characteristics of the materials used in these methods are determined, and recommendations are provided for future improvements and refinements to these two techniques. / Master of Science

No / In the 2007 blind test of crystal structure prediction hosted by the Cambridge Crystallographic Data Centre (CCDC), a hybrid DFT/MM method correctly ranked each of the four experimental structures as having the lowest lattice energy of all the crystal structures predicted for each molecule. The work presented here further validates this hybrid method by optimizing the crystal structures (experimental and submitted) of the first three CCDC blind tests held in 1999, 2001, and 2004. Except for the crystal structures of compound IX, all structures were reminimized and ranked according to their lattice energies. The hybrid method computes the lattice energy of a crystal structure as the sum of the DFT total energy and a van der Waals (dispersion) energy correction. Considering all four blind tests, the crystal structure with the lowest lattice energy corresponds to the experimentally observed structure for 12 out of 14 molecules. Moreover, good geometrical agreement is observed between the structures determined by the hybrid method and those measured experimentally. In comparison with the correct submissions made by the blind test participants, all hybrid optimized crystal structures (apart from compound II) have the smallest calculated root mean squared deviations from the experimentally observed structures. It is predicted that a new polymorph of compound V exists under pressure.

Yes / This paper presents a planar multi-circular loop antenna with a wide impedance bandwidth for next generation mm-wave systems. The proposed antenna comprises three circular rings with a partial ground plane with a square slot. The resonating structure is designed on a 0.254 mm thin RO5880 substrate with a relative permittivity of 2.3. The single element of the proposed design showed a resonance response from 26.5 to 41 GHz, with a peak gain of 4 dBi and radiation efficiency of 96%. The proposed multicircular ring antenna element is transformed into a four-element array system. The array size is kept at 18.25 × 12.5 × 0.254 mm3 with a peak gain of 11 dBi. The antenna array is fabricated and measured using the in-house facility. The simulated and measured results are well agreed upon and are found to be suitable for mm-wave communication systems.

<p dir="ltr">Plant and algae-based biofuels offer a compelling green energy solution, but the utility of biological photosynthesis is limited by inefficiency in energy production. Without the connection between the protein structure and optical spectra, it is challenging to modify optical properties for improving energy production. Chlorophyll proteins (CPs) are the primary work-horses of biological photosynthesis that absorb and transfer solar energy to chemically active reaction centers and control the chemical energy storage process. While the CP structures are well-known, predicting their optical and electronic properties remains a serious challenge. There are computational complications for treating large, electronically coupled molecular pigments embedded in a dynamically structured protein environment. In this work, we aim to address some prominent issues with structure-based optical spectra predictions and the limitations in applying the Frenkel exciton model.</p>

ealizaram-se cálculos ab initio e semi-empíricos em 5-hidrotriptofano (5-OH-trp), 7-aza-triptofano (7-aza-trp) e triptofano (trp), determinando as superfícies de energia potencial (SEP) do estado fundamental (EF) e do primeiro estado excitado (1EE), em função dos ângulos X IND. 1 e X IND. 2, medidos nos diedros N-C IND.alfa-C IND.beta-C IND.gama e C IND.alfa-C IND.beta-C IND.gama- C IND.delta2, respectivamente. Esses compostos foram estudados nos estados de protonação zwitteriônico, neutro e aniônico. A SEP do EF na forma zwitteriônica fo obtida pelo método semi-empírico AM1 e utilizada como referência para os cálculos ab initio. Os cálculos de 1EE foram feitos utilizando o método de Interação de Configurações com excitações simples (ICS) e orbitais internos congelados. As energias de transição entre o EF e o 1EE após as otimizações foram obtidas pelo método semi-empírico INDO/S-CIS, permitindo a obtenção dos espectros teóricos de absorção ótica, pelas energias de transição das geometrias otimizadas no EF, e de fluorescência de estado estacionário, pelas energias de transição das geometrias otimizadas no 1EE. Medidas experimentais dos espectros de absorção ótica e de fluorescência de estado estacionário e resolvida no tempo foram realizadas com o 5-OH-trp e o 7-aza-trp em solução tampão fosfato, pH 7,4. Os decaimentos fluorescentes ajustados a mais de uma exponencial foram estudados em termos das populações relativas de Boltzmann nos EF e 1EE. As taxas do decaimento não-radiativo de transferência de elétrons no 1EE foram obtidas pela implementação computacional da Teoria de Marcus e do Método da Expansão de Perturbação Renormalizada (EPR). Além disso, otimizações de estruturas de estados de transição (ET) na SEP dos 1EE foram realizadas pelo Método Sunchronous Transiti-Guided Quasi-Newton e pelo algoritmo de Berny modificado. Para aproximar as condições experimentais, foram ) realizadas simulações por dinâmica molecular (DM) usando o método híbrido QM/MM no EF do 5-OH-trp na forma zwitteriônica, na presença do solvente aquoso representado explicitamente. Os resultados obtidos dos cálculos ab initio foram usados como referência para o início dessas simulações. As conformações visitadas no EF, os espectros teóricos de absorção ótica e as camadas de solvatação do solvente aquoso em torno do reagente são discutidas. / Semi-empirical and ab-initio calculations were performed on 5-hydroxytryptophan (5-OH-trp), 7-aza-tryptophan (7-aza-trp) and tryptophan (trp). The potential energy surface (PES) of the ground state (GS) and the lowest exited state (1ES) was determined as a function X IND. 1 e X IND. 2 angles corresponding to the dihedrals N-C IND.alfa-C IND.beta-C IND.gama e C IND.alfa-C IND.beta-C IND.gama- C IND.delta2, respectively. The compounds were studied in the zwitterionic, neutral and anionic states. The PES of the GS was obtained using the AM1 semi-empirical method and was used as a reference for the ab-initio calculations. The configuration interaction method with single excitations (CIS) was used for the calculations of the 1ES with frozen internal orbitals. After geometry optimization of GS, the transition energies to 1ES were obtained by INDO/S-CIS, giving the theoretical optical absorption spectrum. Similarly, following the geometry optimization of 1ES, the transition energies to GS were determined, giving the fluorescence emission spectrum. Experimental results were obtained for optical absorption and fluorescence spectra of 5-OH-trp and 7-aza-trp in phosphate buffer solution, pH 7.4. The fluorescence decay of the compounds was also examined. Decay profiles fitted to multiexponential function were analyzed in terms of Boltzmann relative populations in the GS and 1ES. The non-radioactive electron transfer rates in the excited state were obtained by computational implementation of the Marcus Theory with renormalized perturbation expansion method (RPE). In this study, optimizations of the transition states in the PES of the ground and lower excited states were performed by the Synchronous Transit-Guided Quasi-Newton method and the Berny algorithm modified. For further comparison with experimental conditions, molecular dynamic simulations for the zwitterionic 5-OH-trp were performed using the hybrid QM/MM method with explicit representation of the aqueous solvent. To start the simulations the results from ab-initio calculations were used. The conformations for the GS, the theoretical absorption spectrum and the solvation layers were compared to the experimental results

ealizaram-se cálculos ab initio e semi-empíricos em 5-hidrotriptofano (5-OH-trp), 7-aza-triptofano (7-aza-trp) e triptofano (trp), determinando as superfícies de energia potencial (SEP) do estado fundamental (EF) e do primeiro estado excitado (1EE), em função dos ângulos X IND. 1 e X IND. 2, medidos nos diedros N-C IND.alfa-C IND.beta-C IND.gama e C IND.alfa-C IND.beta-C IND.gama- C IND.delta2, respectivamente. Esses compostos foram estudados nos estados de protonação zwitteriônico, neutro e aniônico. A SEP do EF na forma zwitteriônica fo obtida pelo método semi-empírico AM1 e utilizada como referência para os cálculos ab initio. Os cálculos de 1EE foram feitos utilizando o método de Interação de Configurações com excitações simples (ICS) e orbitais internos congelados. As energias de transição entre o EF e o 1EE após as otimizações foram obtidas pelo método semi-empírico INDO/S-CIS, permitindo a obtenção dos espectros teóricos de absorção ótica, pelas energias de transição das geometrias otimizadas no EF, e de fluorescência de estado estacionário, pelas energias de transição das geometrias otimizadas no 1EE. Medidas experimentais dos espectros de absorção ótica e de fluorescência de estado estacionário e resolvida no tempo foram realizadas com o 5-OH-trp e o 7-aza-trp em solução tampão fosfato, pH 7,4. Os decaimentos fluorescentes ajustados a mais de uma exponencial foram estudados em termos das populações relativas de Boltzmann nos EF e 1EE. As taxas do decaimento não-radiativo de transferência de elétrons no 1EE foram obtidas pela implementação computacional da Teoria de Marcus e do Método da Expansão de Perturbação Renormalizada (EPR). Além disso, otimizações de estruturas de estados de transição (ET) na SEP dos 1EE foram realizadas pelo Método Sunchronous Transiti-Guided Quasi-Newton e pelo algoritmo de Berny modificado. Para aproximar as condições experimentais, foram ) realizadas simulações por dinâmica molecular (DM) usando o método híbrido QM/MM no EF do 5-OH-trp na forma zwitteriônica, na presença do solvente aquoso representado explicitamente. Os resultados obtidos dos cálculos ab initio foram usados como referência para o início dessas simulações. As conformações visitadas no EF, os espectros teóricos de absorção ótica e as camadas de solvatação do solvente aquoso em torno do reagente são discutidas. / Semi-empirical and ab-initio calculations were performed on 5-hydroxytryptophan (5-OH-trp), 7-aza-tryptophan (7-aza-trp) and tryptophan (trp). The potential energy surface (PES) of the ground state (GS) and the lowest exited state (1ES) was determined as a function X IND. 1 e X IND. 2 angles corresponding to the dihedrals N-C IND.alfa-C IND.beta-C IND.gama e C IND.alfa-C IND.beta-C IND.gama- C IND.delta2, respectively. The compounds were studied in the zwitterionic, neutral and anionic states. The PES of the GS was obtained using the AM1 semi-empirical method and was used as a reference for the ab-initio calculations. The configuration interaction method with single excitations (CIS) was used for the calculations of the 1ES with frozen internal orbitals. After geometry optimization of GS, the transition energies to 1ES were obtained by INDO/S-CIS, giving the theoretical optical absorption spectrum. Similarly, following the geometry optimization of 1ES, the transition energies to GS were determined, giving the fluorescence emission spectrum. Experimental results were obtained for optical absorption and fluorescence spectra of 5-OH-trp and 7-aza-trp in phosphate buffer solution, pH 7.4. The fluorescence decay of the compounds was also examined. Decay profiles fitted to multiexponential function were analyzed in terms of Boltzmann relative populations in the GS and 1ES. The non-radioactive electron transfer rates in the excited state were obtained by computational implementation of the Marcus Theory with renormalized perturbation expansion method (RPE). In this study, optimizations of the transition states in the PES of the ground and lower excited states were performed by the Synchronous Transit-Guided Quasi-Newton method and the Berny algorithm modified. For further comparison with experimental conditions, molecular dynamic simulations for the zwitterionic 5-OH-trp were performed using the hybrid QM/MM method with explicit representation of the aqueous solvent. To start the simulations the results from ab-initio calculations were used. The conformations for the GS, the theoretical absorption spectrum and the solvation layers were compared to the experimental results

Les méthodes hybrides alliant la mécanique quantique et la mécanique moléculaire (QM/MM) sont des outils adéquats pour traiter des systèmes biologiques. Les phénomènes électroniques souvent étudiés sur des petites molécules ont, dès lors pu être envisagés dans des environnements macromoléculaires. Ce travail explore trois phénomènes électroniques en présence d'un environnement protéique: l'absorption, la capture électronique et les ionisations de coeur. Nous avons employé les derniers développements de la méthode QM/MM {Local Self-Consistent Field} (LSCF) pour traiter la jonction covalente entre la partie QM et la partie MM ainsi que le couplage QM/MM avec le PCM. En premier lieu, nous nous sommes focalisés sur les spectres d'absorption de chromophores présents dans des macromolécules. Nous avons mis au point un couplage entre les méthodes LSCF/MM et PCM pour prendre en compte la polarisation électronique de l'environnement suite à l'absorption d'un photon par le chromophore. Ce modèle, le LSCF/MM\string:ERS, a été testé et validé sur le spectre d'absorption du complexe de squaraine-tétralactame. Une étude plus poussée a ensuite été réalisée sur une protéine fluorescente en décomposant la longueur d'onde d'absorption maximale en trois contributions physiques. Les effets de la substitution du chromophore ont aussi été évalués. Dans une seconde partie, nous avons étudié la capture électronique par un cyclotide contenant trois ponts disulfures, qui, après irradiation, forment des demi-liaisons caractéristiques (2c-3e). La dernière partie est consacrée à la validation de l'approche de la projection asymptotique. Elle a été réalisée dans le cadre d'une étude sur les ionisations de coeur d'un ensemble de molécules pour, par la suite, étudier les ionisations de coeur de la glycine présentes dans des systèmes de plus en plus complexes jusqu'à la Sérum-Albumine Humaine. / Hybrid methods that combine quantum mechanics and molecular mechanics (QM/MM) provide a near-ideal treatment of biological system reactivity and spectroscopy. Many electronic phenomena often studied on small systems can be now forseen in macromolecular surroundings. This work considers the treatment with QM/MM tools of three electronic phenomena in biosystem: absoprtion, electronic attachment and core ionization. Latest developments of the Local Self-Consistent Field formalism (LSCF) have been used to treat delicate covalent junctions between the QM part and the MM part and the coupling of QM/MM and PCM methods. Firstly we have focussed on absorption spectra of chromophores embedded in macromolecules. The combined LSCF/MM and PCM approach have been employed to account for the electronic polarization when the chromophore absorbs one photon. This new method, called LSCF/MM\string:ERS has been tested and validated with the study of the absorption spectra on the squarain-tetralactam complex. Then, we have considered a fluorescent protein and decomposed the maximum absorption wavelength into several physical contributions. We have also analyzed the substitution effect of the chromophore. Secondly, the electronic capture have been studied on a cyclotide containing three disulfide bonds, which forms caracteristic hemi-bond (2c-3e) after irradiation. The last electronic phenomena studied is the core ionization tackled within the framework of the asymptotic projection approach. The latter has been implemented, then tested and validated on a set of molecules. This method have been employed to analyze the specific core ionization of glycine-containing systemes of increasing complexity, up to the Human Serum Albumin

Les flavonoïdes, molécules naturelles possédant des propriétés antiradicalaires et antioxydantes, sont produits au cours de cascades enzymatiques impliquant plusieurs enzymes. Il a récemment été proposé que certaines de ces enzymes s'assembleraient pour former un complexe multienzymatique transitoire, appelé métabolon, ancré à la membrane cellulaire. Cette structure rendrait possible des phénomènes de transfert direct de métabolites d'un site actif à l'autre (substrate channeling), réduisant ainsi les temps de diffusion et minimisant les effets de solvatation/désolvatation du substrat. L'objectif de ce travail est de proposer un premier modèle de ce type de complexe, impliquant trois enzymes de la biosynthèse des flavonoïdes : la dihydroflavonol-4-réductase (DFR), la flavonoïd-3'-hydroxylase (F3’H) et la leucoanthocyanidine réductase (LAR). L'étude de ces complexes moléculaires requiert la mise en œuvre d'une méthodologie multi-échelles basée sur l’utilisation i) de méthodes hybrides QM/MM pour l'étude de la réactivité enzymatique, ii) de simulations de dynamique moléculaire à résolution atomique se déroulant sur des échelles de temps de l'ordre de la microseconde pour estimer des propriétés thermodynamiques et cinétiques, iii) de calculs de docking protéine-protéine en résolution gros grain. L'application des différents niveaux de théorie nous a permis d'établir un premier modèle de métabolon à trois enzymes en interaction avec une membrane cellulaire. / Flavonoids, some natural compounds exhibiting antioxidant properties, are synthesized along enzymatic cascades involving several enzymes. It has been recently proposed that some of these enzymes are involved in the formation of large transient macromolecular edifices, called metabolon, interacting with cellular membrane. Such molecular complexes should allow direct metabolites transfer from one active site to the other (substrate channeling phenomenon), minimizing diffusion time and solvation effects. The present work aims to establish a first model of a metabolon involving 3 enzymes of the flavonoid biosynthesis: the dihydroflavonol 4-reductase (DFR), the flavonoid 3'-hydroxylase (F3'H) and the leucoanthocyanidin reductase (LAR). The study of such large molecular system requires a multiscale approach based on i) hybrid QM/MM methods to decipher enzymatic mechanism, ii) molecular dynamic simulations in microsecond timescale to estimate thermodynamic and kinetic properties and iii) protein-protein docking at coarse-grained resolution. These different levels of theory allow us to establish a first model of a three-enzymes-metabolon in interaction with a model of cellular membrane.

The enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are inhibited by nerve agents such as sarin and tabun. In general, the inhibited enzymes are reactivated by bisquaternary ammonium compounds (oximes). The binding free energies of the oximes; 2-PAM, MMB-4, HI-6, and obidoxime bound to human AChE (hAChE) and human BChE (hBChE) inhibited by sarin and tabun and also to the uninhibited enzymes were calculated using various computational methods. Using thermodynamic integration, the binding free energies of all the inhibited and uninhibited systems of MMB-4 and obidoxime were evaluated. The standard binding free energies (dA) were more negative than the experimental values due to limitations of the ff99 forcefield. The RMS error of dA for the inhibited systems of MMB-4 was 2.1 kcal/mol, and for obidoxime systems it was 4.8 kcal/mol with respect to the experimental free energies. The binding enthalpies calculated using MM-GBSA and MM-PBSA methods for 2-PAM, MMB-4, HI-6, and obidoxime systems were negative, except for hBChE-sarin-MMB-4 and hBChE-sarin-obidoxime. For all the systems the TdS values calculated using normal mode analysis were equal to or lower in magnitude than their corresponding binding enthalpies. As a result, the estimated free energies were positive for most of the systems. Clearly, the present algorithms cannot effectively estimate the binding entropies for a protein-ligand system. Met81 has commonly shown favorable interactions, and lysine or arginine exhibited unfavorable interactions with the reactivator in all the systems. Second, the interactions between chloropyrifos-oxon (Cpo) and experimentally tested neutral and monopyridinium oximes bound to the Q192 or R192 polymorphs of human paraoxonase1 (hPON1) were studied. The equilibrated Q192 and R192 hPON1 were structurally different than the crystal structure of recombinant PON1. The neutral oximes have shown more favorable interactions with Cpo in Q192 hPON1 + Cpo system compared to R192 hPON1 + Cpo. Whereas the monopyridinium oximes interacted more affectively with Cpo in R192 hPON1 than Q192 hPON1. The relative deprotonation energy of the monopyridinium oxime was lower than the neutral oxime. Hence, the monopyridinium oxime can hydrolyze an organophosphate at a higher rate than a neutral oxime.

En sjukdom kan många gånger härledas till en kaskadereaktion mellan proteiner, co-faktorer och substrat. Denna kaskadreaktion blir många gånger målet för att behandla sjukdomen med läkemedel. För att designa nya läkemedelsmoleyler används vanligen datorbaserade verktyg. Denna design av läkemedelsmolekyler drar stor nytta av att målproteinet är känt och då framförallt dess tredimensionella (3D) struktur. Är 3D-strukturen känd kan man utföra så kallad struktur- och datorbaserad molekyldesign, 3D-geometrin (f.f.a. för inbindningsplatsen) blir en vägledning för designen av en ny molekyl. Många faktorer avgör interaktionen mellan en molekyl och bindningsplatsen, till exempel fysikalisk-kemiska egenskaper hos molekylen och bindningsplatsen, flexibiliteten i molekylen och målproteinet, och det omgivande lösningsmedlet. För att strukturbaserad molekyldesign ska fungera väl måste två viktiga steg utföras: i) 3D anpassning av molekyler till bindningsplatsen i ett målprotein (s.k. dockning) och ii) prediktion av molekylers affinitet för bindningsplatsen. Huvudsyftena med arbetet i denna avhandling var som följer: i) skapa modeler för att prediktera affiniteten mellan en molekyl och bindningsplatsen i ett målprotein; ii) förfina molekyl-protein-geometrin som skapas vid 3D-anpassning mellan en molekyl och bindningsplatsen i ett målprotein (s.k. dockning); iii) karaktärisera proteiner och framför allt deras sekundärstruktur; iv) bedöma effekten av olika matematiska beskrivningar av lösningsmedlet för förfining av 3D molekyl-protein-geometrin skapad vid dockning och prediktion av molekylers affinitet för proteiners bindningsfickor. Ett övergripande syfte var att använda kemometriska metoder för modellering och dataanalys på de ovan nämnda punkterna. För att sammanfatta så presenterar denna avhandling metoder och resultat som är användbara för strukturbaserad molekyldesign. De rapporterade resultaten visar att det är möjligt att skapa kemometriska modeler för prediktion av molekylers affinitet för bindningsplatsen i ett protein och att dessa presterade lika bra som andra vanliga metoder. Dessutom kunde kemometriska modeller skapas för att beskriva effekten av hur inställningarna för olika parametrar i dockningsprogram påverkade den 3D molekyl-protein-geometrin som dockingsprogram skapade. Vidare kunde kemometriska modeller andvändas för att öka förståelsen för deskriptorer som beskrev sekundärstrukturen i proteiner. Förfining av molekyl-protein-geometrin skapad genom dockning gav liknande och ickesignifikanta resultat oberoende av vilken matematisk modell för lösningsmedlet som användes, förutom för ett fåtal (sex av 30) fall. Däremot visade det sig att användandet av en förfinad geometri var värdefullt för prediktion av molekylers affinitet för bindningsplatsen i ett protein. Förbättringen av prediktion av affintitet var markant då en Poisson-Boltzmann beskrivning av lösningsmedlet användes; jämfört med prediktionerna gjorda med ett dockningsprogram förbättrades korrelationen mellan beräknad affintiet och uppmätt affinitet med 0,7 (R2). / A disease is often associated with a cascade reaction pathway involving proteins, co-factors and substrates. Hence to treat the disease, elements of this pathway are often targeted using a therapeutic agent, a drug. Designing new drug molecules for use as therapeutic agents involves the application of methods collectively known as computer-aided molecular design, CAMD. When the three dimensional (3D) geometry of a macromolecular target (usually a protein) is known, structure-based CAMD is undertaken and structural information of the target guides the design of new molecules and their interactions with the binding sites in targeted proteins. Many factors influence the interactions between the designed molecules and the binding sites of the target proteins, such as the physico-chemical properties of the molecule and the binding site, the flexibility of the protein and the ligand, and the surrounding solvent. In order for structure-based CAMD to be successful, two important aspects must be considered that take the abovementioned factors into account. These are; i) 3D fitting of molecules to the binding site of the target protein (like fitting pieces of a jigsaw puzzle), and ii) predicting the affinity of molecules to the protein binding site. The main objectives of the work underlying this thesis were: to create models for predicting the affinity between a molecule and a protein binding site; to refine the geometry of the molecule-protein complex derived by or in 3D fitting (also known as docking); to characterize the proteins and their secondary structure; and to evaluate the effects of different generalized-Born (GB) and Poisson-Boltzmann (PB) implicit solvent models on the refinement of the molecule-protein complex geometry created in the docking and the prediction of the molecule-to-protein binding site affinity. A further objective was to apply chemometric methodologies for modeling and data analysis to all of the above. To summarize, this thesis presents methodologies and results applicable to structure-based CAMD. Results show that predictive chemometric models for molecule-to-protein binding site affinity could be created that yield comparable results to similar, commonly used methods. In addition, chemometric models could be created to model the effects of software settings on the molecule-protein complex geometry using software for molecule-to-binding site docking. Furthermore, the use of chemometric models provided a more profound understanding of protein secondary structure descriptors. Refining the geometry of molecule-protein complexes created through molecule-to-binding site docking gave similar results for all investigated implicit solvent models, but the geometry was significantly improved in only a few examined cases (six of 30). However, using the geometry-refined molecule-protein complexes was highly valuable for the prediction of molecule-to-binding site affinity. Indeed, using the PB solvent model it yielded improvements of 0.7 in correlation coefficients (R2) for binding affinity parameters of a set of Factor Xa protein drug molecules, relative to those obtained using the fitting software.