The Role of Molecular Conformation and Polarizable Embedding for One- and Two-Photon Absorption of Disperse Orange 3 in Solution

Solvent effects on the one- and two-photon absorption (IPA and 2PA) of disperse orange 3 (DO3) in dimethyl sulfoxide (DMSO) are studied using a discrete polarizable embedding (PE) response theory. The scheme comprises a quantum region containing the chromophore and an atomically granulated classical region for the solvent accounting for full interactions within and between the two regions. Either classical molecular dynamics (MD) or hybrid Car-Parrinello (CP) quantum/classical (QM/MM) molecular dynamics simulations are employed to describe the solvation of DO3 in DMSO, allowing for an analysis of the effect of the intermolecular short-range repulsion, long-range attraction, and electrostatic interactions on the conformational changes of the chromophore and also the effect of the solute-solvent polarization. PE linear response calculations are performed to verify the character, solvatochromic shift, and overlap of the two lowest energy transitions responsible for the linear absorption spectrum of DO3 in DMSO in the visible spectral region. Results of the PE linear and quadratic response calculations, performed using uncorrelated solute-solvent configurations sampled from either the classical or hybrid CP QM/MM MD simulations, are used to estimate the width of the line shape function of the two electronic lowest energy excited states, which allow a prediction of the 2PA cross-sections without the use of empirical parameters. Appropriate exchange-correlation functionals have been employed in order to describe the charge-transfer process following the electronic transitions of the chromophore in solution.

A simple analysis of the influence of the solvent-induced electronic polarization on the N-15 magnetic shielding of pyridine in water

Electronic polarization induced by the interaction of a reference molecule with a liquid environment is expected to affect the magnetic shielding constants. Understanding this effect using realistic theoretical models is important for proper use of nuclear magnetic resonance in molecular characterization. In this work, we consider the pyridine molecule in water as a model system to briefly investigate this aspect. Thus, Monte Carlo simulations and quantum mechanics calculations based on the B3LYP/6-311++G (d,p) are used to analyze different aspects of the solvent effects on the N-15 magnetic shielding constant of pyridine in water. This includes in special the geometry relaxation and the electronic polarization of the solute by the solvent. The polarization effect is found to be very important, but, as expected for pyridine, the geometry relaxation contribution is essentially negligible. Using an average electrostatic model of the solvent, the magnetic shielding constant is calculated as -58.7 ppm, in good agreement with the experimental value of -56.3 ppm. The explicit inclusion of hydrogen-bonded water molecules embedded in the electrostatic field of the remaining solvent molecules gives the value of -61.8 ppm.

Progress toward chemical accuracy in the computer simulation of condensed phase reactions.

We describe a procedure for the generation of chemically accurate computer-simulation models to study chemical reactions in the condensed phase. The process involves (i) the use of a coupled semiempirical quantum and classical molecular mechanics method to represent solutes and solvent, respectively; (ii) the optimization of semiempirical quantum mechanics (QM) parameters to produce a computationally efficient and chemically accurate QM model; (iii) the calibration of a quantum/classical microsolvation model using ab initio quantum theory; and (iv) the use of statistical mechanical principles and methods to simulate, on massively parallel computers, the thermodynamic properties of chemical reactions in aqueous solution. The utility of this process is demonstrated by the calculation of the enthalpy of reaction in vacuum and free energy change in aqueous solution for a proton transfer involving methanol, methoxide, imidazole, and imidazolium, which are functional groups involved with proton transfers in many biochemical systems. An optimized semiempirical QM model is produced, which results in the calculation of heats of formation of the above chemical species to within 1.0 kcal/mol (1 kcal = 4.18 kJ) of experimental values. The use of the calibrated QM and microsolvation QM/MM (molecular mechanics) models for the simulation of a proton transfer in aqueous solution gives a calculated free energy that is within 1.0 kcal/mol (12.2 calculated vs. 12.8 experimental) of a value estimated from experimental pKa values of the reacting species.

Modelagem molecular voltada para a construção de um nanobiossensor para detecção do herbicida Imazaquin

In this study, our goal was develop and describe a molecular model of the enzyme-inhibiting interaction which can be used for an optimized projection of a Microscope Force Atomic nanobiosensor to detect pesticides molecules, used in agriculture, to evaluate its accordance with limit levels stipulated in valid legislation for its use. The studied herbicide (imazaquin) is a typical member of imidazolinone family and is an inhibitor of the enzymatic activity of Acetohydroxiacid Synthase (AHAS) enzyme that is responsible for the first step of pathway for the synthesis of side-chains in amino acids. The analysis of this enzyme property in the presence of its cofactors was made to obtain structural information and charge distribution of the molecular surface to evaluate its capacity of became immobilized on the Microscopy Atomic Force tip. The computational simulation of the system, using Molecular Dynamics, was possible with the force-field parameters for the cofactor and the herbicides obtained by the online tool SwissParam and it was implemented in force-field CHARMM27, used by software GROMACS; then appropriated simulations were made to validate the new parameters. The molecular orientation of the AHAS was defined based on electrostatic map and the availability of the herbicide in the active site. Steered Molecular Dynamics (SMD) Simulations, followed by quantum mechanics calculations for more representative frames, according to the sequential QM/MM methodology, in a specific direction of extraction of the herbicide from the active site. Therefore, external harmonic forces were applied with similar force constants of AFM cantilever for to simulate herbicide detection experiments by the proposed nanobiosensor. Force value of 1391 pN and binding energy of -14048.52 kJ mol-1 were calculated.

The Catalytic Mechanism of the Marine-Derived Macrocyclase, PATGmac

Acknowledgements This work received financial support from the European Union (FEDER funds through COMPETE) and National Funds (FCT, Fundação para a Ciência e Tecnologia) through Projects EXCL/QEQ-COM/ 0394/2012, EXCL-II/QEQ-COM/0394/2012, and Pest-C/EQB/LA0006/2013. NFB would like to thank the Fundação para a Ciência e a Tecnologia (FCT) for her IF starting grant (IF/01355/2014).

Magnetic properties of paramagnetic systems : density functional studies

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Magnetic properties of paramagnetic systems : density functional studies

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

A disappearing act performed by magnesium: the nucleotide exchange mechanism of Ran GTPase by Quantum mechanics/Molecular mechanics studies

The Ran GTPase protein is a guanine nucleotide-binding protein (GNBP) with an acknowledged profile in cancer onset, progression and metastases. The complex mechanism adopted by GNBPs in exchanging GDP for GTP is an intriguing process and crucial for Ran viability. The successful completion of the process is a fundamental aspect of propagating downstream signalling events. QM/MM molecular dynamics simulations were employed in this study to provide a deeper mechanistic understanding of the initiation of nucleotide exchange in Ran. Results indicate significant disruption of the metal-binding site upon interaction with RCC1 (the Ran guanine nucleotide exchange factor), overall culminating in the prominent shift of the divalent magnesium ion. The observed ion drifting is reasoned to occur as a consequence of the complex formation between Ran and RCC1 and is postulated to be a critical factor in the exchange process adopted by Ran. This is the first report to observe and detail such intricate dynamics for a protein in Ras superfamily.

Phosphorylation Mechanism of Phosphomevalonate Kinase: Implications for Rational Engineering of Isoprenoid Biosynthetic Pathway Enzymes

Mevalonate pathway is of important clinical, pharmaceutical and biotechnological relevance. However, lack of the understanding of the phosphorylation mechanism of the kinases in this pathway has limited rationally engineering the kinases in industry. Here the phosphorylation reaction mechanism of a representative kinase in the mevalonate pathway, phosphomevalonate kinase, was studied by using molecular dynamics and hybrid QM/MM methods. We find that a conserved residue (Ser106) is reorientated to anchor ATP via a stable H-bond interaction. In addition, Ser213 located on the α-helix at the catalytic site is repositioned to further approach the substrate, facilitating the proton transfer during the phosphorylation. Furthermore, we elucidate that Lys101 functions to neutralize the negative charge developed at the β-, γ-bridging oxygen atom of ATP during phosphoryl transfer. We demonstrate that the dissociative catalytic reaction occurs via a direct phosphorylation pathway. This is the first study on the phosphorylation mechanism of a mevalonate pathway kinase. The elucidation of the catalytic mechanism not only sheds light on the common catalytic mechanism of GHMP kinase superfamily, but also provides the structural basis for engineering the mevalonate pathway kinases to further exploit their applications in the production of a wide range of fine chemicals such as biofuels or pharmaceuticals. 

Multi-scale approaches to Food Sciences: computational QM and MM explorations at the microscopic level

L'obiettivo principale della politica di sicurezza alimentare è quello di garantire la salute dei consumatori attraverso regole e protocolli di sicurezza specifici. Al fine di rispondere ai requisiti di sicurezza alimentare e standardizzazione della qualità, nel 2002 il Parlamento Europeo e il Consiglio dell'UE (Regolamento (CE) 178/2002 (CE, 2002)), hanno cercato di uniformare concetti, principi e procedure in modo da fornire una base comune in materia di disciplina degli alimenti e mangimi provenienti da Stati membri a livello comunitario. La formalizzazione di regole e protocolli di standardizzazione dovrebbe però passare attraverso una più dettagliata e accurata comprensione ed armonizzazione delle proprietà globali (macroscopiche), pseudo-locali (mesoscopiche), ed eventualmente, locali (microscopiche) dei prodotti alimentari. L'obiettivo principale di questa tesi di dottorato è di illustrare come le tecniche computazionali possano rappresentare un valido supporto per l'analisi e ciò tramite (i) l’applicazione di protocolli e (ii) miglioramento delle tecniche ampiamente applicate. Una dimostrazione diretta delle potenzialità già offerte dagli approcci computazionali viene offerta nel primo lavoro in cui un virtual screening basato su docking è stato applicato al fine di valutare la preliminare xeno-androgenicità di alcuni contaminanti alimentari. Il secondo e terzo lavoro riguardano lo sviluppo e la convalida di nuovi descrittori chimico-fisici in un contesto 3D-QSAR. Denominata HyPhar (Hydrophobic Pharmacophore), la nuova metodologia così messa a punto è stata usata per esplorare il tema della selettività tra bersagli molecolari strutturalmente correlati e ha così dimostrato di possedere i necessari requisiti di applicabilità e adattabilità in un contesto alimentare. Nel complesso, i risultati ci permettono di essere fiduciosi nel potenziale impatto che le tecniche in silico potranno avere nella identificazione e chiarificazione di eventi molecolari implicati negli aspetti tossicologici e nutrizionali degli alimenti.

Monte Carlo modeling of a 4 mm conical collimator for a Novalis Tx Linear Accelerator

The work presented in this poster outlines the steps taken to model a 4 mm conical collimator (BrainLab, Germany) on a Novalis Tx linear accelerator (Varian, Palo Alto, USA) capable of producing a 6MV photon beam for treatment of Stereotactic Radiosurgery (SRS) patients. The verification of this model was performed by measurements in liquid water and in virtual water. The measurements involved scanning depth dose and profiles in a water tank plus measurement of output factors in virtual water using Gafchromic® EBT3 film.

Verifying a Student Engagement, Success and Retention Maturity Model (SESR-MM): A reality check of the model using data derived from three universities

Australian higher education institutions (HEIs) have entered a new phase of regulation and accreditation which includes performance-based funding relating to the participation and retention of students from social and cultural groups previously underrepresented in higher education. However, in addressing these priorities, it is critical that HEIs do not further disadvantage students from certain groups by identifying them for attention because of their social or cultural backgrounds, circumstances which are largely beyond the control of students. In response, many HEIs are focusing effort on university-wide approaches to enhancing the student experience because such approaches will enhance the engagement, success and retention of all students, and in doing so, particularly benefit those students who come from underrepresented groups. Measuring and benchmarking student experiences and engagement that arise from these efforts is well supported by extensive collections of student experience survey data. However no comparable instrument exists that measures the capability of institutions to influence and/or enhance student experiences where capability is an indication of how well an organisational process does what it is designed to do (Rosemann & de Bruin, 2005). We have proposed that the concept of a maturity model (Marshall, 2010; Paulk, 1999) may be useful as a way of assessing the capability of HEIs to provide and implement student engagement, success and retention activities and we are currently articulating a Student Engagement, Success and Retention Maturity Model (SESR-MM), (Clarke, Nelson & Stoodley, 2012; Nelson, Clarke & Stoodley, 2012). Our research aims to address the current gap by facilitating the development of an SESR-MM instrument that aims (i) to enable institutions to assess the capability of their current student engagement and retention programs and strategies to influence and respond to student experiences within the institution; and (ii) to provide institutions with the opportunity to understand various practices across the sector with a view to further improving programs and practices relevant to their context. Our research extends the generational approach which has been useful in considering the evolutionary nature of the first year experience (FYE) (Wilson, 2009). Three generations have been identified and explored: First generation approaches that focus on co-curricular strategies (e.g. orientation and peer programs); Second generation approaches that focus on curriculum (e.g. pedagogy, curriculum design, and learning and teaching practice); and third generation approaches—also referred to as transition pedagogy—that focus on the production of an institution-wide integrated holistic intentional blend of curricular and co-curricular activities (Kift, Nelson & Clarke, 2010). Our research also moves beyond assessments of students’ experiences to focus on assessing institutional processes and their capability to influence student engagement. In essence, we propose to develop and use the maturity model concept to produce an instrument that will indicate the capability of HEIs to manage and improve student engagement, success and retention programs and strategies. The issues explored in this workshop are (i) whether the maturity model concept can be usefully applied to provide a measure of institutional capability for SESR; (ii) whether the SESR-MM can be used to assess the maturity of a particular set of institutional practices; and (iii) whether a collective assessment of an institution’s SESR capabilities can provide an indication of the maturity of the institution’s SESR activities. The workshop will be approached in three stages. Firstly, participants will be introduced to the key characteristics of maturity models, followed by a discussion of the SESR-MM and the processes involved in its development. Secondly, participants will be provided with resources to facilitate the development of a maturity model and an assessment instrument for a range of institutional processes and related practices. In the final stage of the workshop, participants will “assess” the capability of these practices to provide a collective assessment of the maturity of these processes. References Australian Council for Educational Research. (n.d.). Australasian Survey of Student Engagement. Retrieved from http://www.acer.edu.au/research/ausse/background Clarke, J., Nelson, K., & Stoodley, I. (2012, July). The Maturity Model concept as framework for assessing the capability of higher education institutions to address student engagement, success and retention: New horizon or false dawn? A Nuts & Bolts presentation at the 15th International Conference on the First Year in Higher Education, “New Horizons,” Brisbane, Australia. Department of Education, Employment and Workplace Relations. (n.d.). The University Experience Survey. Advancing quality in higher education information sheet. Retrieved from http://www.deewr.gov.au/HigherEducation/Policy/Documents/University_Experience_Survey.pdf Kift, S., Nelson, K., & Clarke, J. (2010) Transition pedagogy - a third generation approach to FYE: A case study of policy and practice for the higher education sector. The International Journal of the First Year in Higher Education, 1(1), pp. 1-20. Marshall, S. (2010). A quality framework for continuous improvement of e-Learning: The e-Learning Maturity Model. Journal of Distance Education, 24(1), 143-166. Nelson, K., Clarke, J., & Stoodley, I. (2012). An exploration of the Maturity Model concept as a vehicle for higher education institutions to assess their capability to address student engagement. A work in progress. Submitted for publication. Paulk, M. (1999). Using the Software CMM with good judgment, ASQ Software Quality Professional, 1(3), 19-29. Wilson, K. (2009, June–July). The impact of institutional, programmatic and personal interventions on an effective and sustainable first-year student experience. Keynote address presented at the 12th Pacific Rim First Year in Higher Education Conference, “Preparing for Tomorrow Today: The First Year as Foundation,” Townsville, Australia. Retrieved from http://www.fyhe.com.au/past_papers/papers09/ppts/Keithia_Wilson_paper.pdf

Measurement of the first neutron diffraction peak of D2O flowing in a 2 mm diameter aluminium tube as a function of temperature

A pilot experiment was performed using the WOMBAT powder diffraction instrument at ANSTO in which the first neutron diffraction peak (Q0) was measured for D2O flowing in a 2 mm internal diameter aluminium tube. Measurements of Q0 were made at -9, 4.3, 6.9, 12, 18.2 and 21.5 °C. The D2O was circulated using a siphon with water in the lower reservoir returned to the upper reservoir using a small pump. This enabled stable flow to be maintained for several hours. For example, if the pump flow increased slightly, the upper reservoir level rose, increasing the siphon flow until it matched the return flow. A neutron wavelength of 2.4 Å was used and data integrated over 60 minutes for each temperature. A jet of nitrogen from a liquid N2 Dewar was directed over the aluminium tube to vary water temperature. After collection of the data, the d spacing of the aluminium peaks was used to calculate the temperature of the aluminium within the neutron beam and therefore was considered to be an accurate measure of water temperature within the beam. Sigmaplot version 12.3 was used to fit a Weibull five parameter peak fit to the first neutron diffraction peak. The values of Q0 obtained in this experiment showed an increase with temperature consistent with data in the literature [1] but were consistently higher than published values for bulk D20. For example at 21.5 °C we obtained a value of 2.008 Å-1 for Q0 compared to a literature value of 1.988 Å-1 for bulk D2O at 20 °C, a difference of 1%. Further experiments are required to see if this difference is real or artifactual.

VFT performance of a 180/110 mm co-axial gap in SF6 up to 4 bar absolute

Disconnector switch operation in GIS generates VFT voltages in the system. It is important, for insulation co-ordination purposes, to obtain accurate VFT V-t data for typical gap geometries found in GIS. This paper presents experimentally obtained VFT V-t data for a 180/1 lOmm co-axial gap. The VFT has a time to first peak of 35 ns and a oscillation frequency of 13,6 MHz. Due to the location of the voltage divider in a compartment adjacent to the gap, a correction factor of 1.1 is used to relate the measured breakdown voltage to that in the gap. Positive polarity VFT V-t data is presented for 1, 2, 3 and 4 bar absolute and negative polarity VFT data for 3 and 4 bar absolute. Two methods of generating the VFT's are used. The first is to power up the test transformer at power frequency. The second is to generate a switching impulse by discharging a capacitor into the primary of the test transformer.