Computational methods conformational analysis

There is a lot of confusion over the meaning of the terms theoretical chemistry, computational chemistry and molecular modelling. Indeed, many practitioners use all three labels to describe aspects of their research, as the occasion demands "Theoretical chemistry is often considered synonymous with quantum mechanics, whereas computational chemistry encompasses not only quantum mechanics but also molecular mechaiucs, minimisation, simulations, conformational analysis and other computer-based methods for understanding and predicting the behaviour of molecular systems. Molecular modellers use all of these methods and so we shall not concern ourselves with semantics but rather shall consider any theoretical or computational tecluiique that provides insight into the behaviour of molecular systems to be an example of molecular modelling. If a distinction has to be... 

With the development of accurate computational methods for generating 3D conformations of chemical structures, QSAR approaches that employ 3D descriptors have been developed to address the problems of 2D QSAR techniques, e.g., their inability to distinguish stereoisomers. The examples of 3D QSAR include molecular shape analysis (MSA) [34], distance geometry [35,36], and Voronoi techniques [37]. 

This approach of combining shape-matching and conformahonal analysis proved a useful complement to HTS. Some of the compounds identified by the computational screen were not detected in the original experimental screen. This was because their relative weak activity was difficult to separate from the noise of the assay. Nonetheless, these compounds had different scaffolds (i.e. were lead-hops ) compared to the previously known inhibitor. The key contribution from conformational analysis was that the newly discovered inhibitors were not found by the corresponding searches based on 2D methods. 

The currently available quantum chemical computational methods and computer programs have not been utilized to their potential in elucidating the electronic origin of zeolite properties. As more and more physico-chemical methods are used successfully for the description and characterization of zeolites, (e.g. (42-45)), more questions will also arise where computational quantum chemistry may have a useful contribution towards the answer, e.g. in connection with combined approaches where zeolites and metal-metal bonded systems (e.g. (46,47)) are used in combination. The spectacular recent and projected future improvements in computer technology are bound to enlarge the scope of quantum chemical studies on zeolites. Detailed studies on optimum intercavity locations for a variety of molecules, and calculations on conformation analysis and reaction mechanism in zeolite cavities are among the promises what an extrapolation of current developments in computational quantum chemistry and computer technology holds out for zeolite chemistry. 

The size of the atoms and the rigidity of the bonds, bond angles, torsions, etc. are determined empirically, that is, they are chosen to reproduce experimental data. Electrons are not part of the MM description, and as a result, several key chemical phenomena cannot be reproduced by this method. Nevertheless, MM methods are orders of magnitude cheaper from a computational point of view than quantum mechanical (QM) methods, and because of this, they have found a preferential position in a number of areas of computational chemistry, like conformational analysis of organic compounds or molecular dynamics. 

The purpose of the present work is to claim that a third method exists in quantum chemistry for the dynamical conformational analysis of large molecules. We challenged that it would be possible to design such a new route by skilfully using a very simple micro-computing dynamic system in order to reduce the n-dimensional problem to a much smaller one, the size of which would be then compatible with the currently low budget of an academic laboratory. 

Computational chemistry methodology is finding increasing application to the design of new flavoring agents. This chapter surveys several useful techniques linear free energy relationships, quantitative structure-activity relationships, conformational analysis, electronic structure calculations, and statistical methods. Applications to the study of artificial sweeteners are described. 

A review of the Journal of Physical Chemistry A, volume 110, issues 6 and 7, reveals that computational chemistry plays a major or supporting role in the majority of papers. Computational tools include use of large Gaussian basis sets and density functional theory, molecular mechanics, and molecular dynamics. There were quantum chemistry studies of complex reaction schemes to create detailed reaction potential energy surfaces/maps, molecular mechanics and molecular dynamics studies of larger chemical systems, and conformational analysis studies. Spectroscopic methods included photoelectron spectroscopy, microwave spectroscopy circular dichroism, IR, UV-vis, EPR, ENDOR, and ENDOR induced EPR. The kinetics papers focused on elucidation of complex mechanisms and potential energy reaction coordinate surfaces. 

A method is presented for the direct computation of statistical weights from conformational analysis for the RIS analysis of PDMS. 

The following definition of computational chemistry was published in 1985 (6) quantitative modeling of chemical behavior on a computer by the formalisms of theoretical chemistry. Some quantum theoreticians naturally would like to see computational chemistry as a subset of their field (7). However, today the number of scientists employed as computational chemists well exceeds the number employed as theoreticians (8). A recent textbook author (9) views computational chemistry as encompassing not only quantum mechanics, but also molecular mechanics, [energy] minimization, simulations, conformational analysis, and other computer-based methods for understanding and predicting the behavior of molecular systems. ... 

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