Integrated computational approach

EPR Spectra of Organic Free Radicals in Solution from an Integrated Computational Approach... 

The present contribution is devoted to the development and application of an integrated computational approach to the EPR spectra of organic radicals in solution. Using nitrox-ides as test cases we have shown how the magnetic properties are modulated by structural, environmental and dynamical effects. The use of methods able to provide accurate results for all these contributions is thus mandatory for a reliable calculation of magnetic parameters. 

Then, as case study, we consider the glycine and glycyl radicals (Fig. 6.2) in solution. As mentioned above, the calculation of magnetic tensors needs to take into account the several factors such as the geometries, environmental effects, and dynamical effects (vibrational averaging from intramolecular vibrations and/or solvent librations). We use an integrated computational approach where the molecular... 

From the bulk of publications and preceding sections in this and other chapters of this book, it is apparent that it may be useful to build an integrated computational approach that will (i) predict which transporters will have affinity for novel xenobiotic compounds, (ii) identify whether the role of one or more human transporters (and their polymorphisms) may be a risk factor for patients and drug developers, (iii) propose potential toxic effects, and (iv) enable the combination of predicted and experimental data (gene expression, in vitro biology, etc.) for drug transporters (Figure 14.6). 

Livny, J Fogel, M. A., Davis, B. M., and Waldor, M. K. (2005) sRNAPredict an integrative computational approach to identify sRNAs in bacterial genomes. Nucleic Acids Res. 33, 4096 1105. 

ABSTRACT. The reaction path Hamiltonian model for the dynamics of general polyatomic systems is reviewed. Various dynamical treatments based on it are discussed, from the simplest statistical approximations (e.g., transition state theory, RRKM, etc.) to rigorous path integral computational approaches that can be applied to chemical reactions in polyatomic systems. Examples are presented which illustrate this menu of dynamical possibilities. 

Today the spectral profiles can be simulated for any motional regime by a numerical integration of the stochastic Liouville equation, as discussed in Chapter 12 and in the references therein. The noticeable improvement in the techniques of calculation of the magnetic parameters and their dependence on the solvent, and of the minimum energy conformation of the molecules, have opened the possibility of an integrated computational approach. Since it gives calculated spectral profiles completely determined by the molecular and physical properties of the radical and of the solvent at a given temperature, this method is a step forward in the direction of a sound interpretation of complex spectra. 

Spectroscopic experiments have always required a strong theoretical support for the interpretation of data in terms of equilibrium molecular geometry, vibrational force fields, energy and nature of the different electronic excited states, and so on. Nowadays the trend toward the study of molecular systems of ever-increasing complexity in terms of dimensionality and/or flexibility makes the theoretical support to experiments even more important. This results in the development of integrated computational approaches that combine accurate determination of structural and electronic properties and/or expUcit description of their time evolution, to be compared to state-of-the-art experimental results, either in the frequency or time high resolution. 

Pavone M et al (2007) Interplay of intrinsic, environmental, and dynamic effects in tuning the EPR parameters of nitroxides further insights from an integrated computational approach. J Phys Chem B 111 8928-8939... 

Myrianihopoulos, V, Magiatis, P., Ferandin, Y, Skaltsounis, A.L., Meijer, L., and Mikros, E. (2007) An integrated computational approach to the phenomenon of potent and selective inhibition of aurora kinases B and C by a series of 7-substituted indirubins. /. Med. Chem., 50,4027-4037. 

Tuckerman M E and Hughes A 1998 Path integral molecular dynamics a computational approach to quantum statistical mechanics Classical and Quantum Dynamics In Condensed Phase Simulations ed B J Berne, G Ciccotti and D F Coker (Singapore World Scientific) pp 311-57... 

For reasons of space and because of their prime importance, we focus here on free energy calculations based on detailed molecular dynamics (MD) or Monte Carlo (MC) simulations. However, several other computational approaches exist to calculate free energies, including continuum dielectric models and integral equation methods [4,14]. 

The first dynamical simulation of a protein based on a detailed atomic model was reported in 1977. Since then, the uses of various theoretical and computational approaches have contributed tremendously to our understanding of complex biomolecular systems such as proteins, nucleic acids, and bilayer membranes. By providing detailed information on biomolecular systems that is often experimentally inaccessible, computational approaches based on detailed atomic models can help in the current efforts to understand the relationship of the strucmre of biomolecules to their function. For that reason, they are now considered to be an integrated and essential component of research in modern biology, biochemistry, and biophysics. 

In conclusion, it is likely that computational approaches for metabolism prediction will continue to be developed and integrated with other algorithms for pharmaceutical research and development, which may in turn ultimately aid in their more widespread use in both industry and academia. Such models may already be having some impact when integrated with bioanalytical approaches to narrow the search for possible metabolites that are experimentally observed. Software that can be updated by the user as new metabolism information becomes available would also be of further potential value. The held of metabolism prediction has therefore advanced rapidly over the past decade, and it will be important to maintain this momentum in the future as the hndings from crystal structures for many discrete metabolic enzymes are integrated with the diverse types of computational models already derived. 

The everlasting need for better experimental tools and theoretical methods to explore the field of carbocation chemistry had also a significant influence on the further development of ab initio methods for the calculation of NMR shielding and indirect spin-spin coupling constants. Carbocation chemistry thus serves as a forerunner for a close integration of experimental and computational approaches in all areas of chemistry. 

Bioinformatics is using computational approaches to solve biomedical problems and to improve the communication, understanding, and management of biomedical information (5). Because of the information overflow, how to integrate biomedical... 

An analogy may be drawn between the phase behavior of weakly attractive monodisperse dispersions and that of conventional molecular systems provided coalescence and Ostwald ripening do not occur. The similarity arises from the common form of the pair potential, whose dominant feature in both cases is the presence of a shallow minimum. The equilibrium statistical mechanics of such systems have been extensively explored. As previously explained, the primary difficulty in predicting equilibrium phase behavior lies in the many-body interactions intrinsic to any condensed phase. Fortunately, the synthesis of several methods (integral equation approaches, perturbation theories, virial expansions, and computer simulations) now provides accurate predictions of thermodynamic properties and phase behavior of dense molecular fluids or colloidal fluids [1]. 

In this chapter, our objective will be to integrate theory and experiment in relating chemical and physical properties of these three classes of compounds to electronic and structural factors. We will begin with an overview and comparison of some computational approaches. 

This chapter has addressed some of the critical issues and questions for computational approaches to understanding, modeling, and predicting developmental toxicity. Recent advances in computing power allow for the integration and correlation of vast amounts of data. This greatly extends our ability to identify and understand... 

Integrating Computational Chemistry into the Physical Chemistry Laboratory Curriculum A Wet Lab/Dry Lab Approach 91... 

Since we follow an analytical, quantitative, and open-source computational approach, our pharmaceutical product/process and project management method and software toolset are implemented as (Internet browser readable) MS-Excel spreadsheets, integrated with several hyperlinks to the rule base and to optional 2D video and 3D virtual-reality objects for visualization. 

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