Simulations conformational analysis molecular

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... 

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. ... 

Grassy, G. and Lahana, R. (1993). Statistical Analysis and Shape Recognition Applications to MD Simulations, Conformational Analysis and Structure-Activity Relationships. In Trends in QSAR and Molecular Modelling 92 (Wermuth, C.G., ed.), ESCOM, Leiden (The Netherlands), pp. 216-219. 

Other methods which are applied to conformational analysis and to generating multiple conformations and which can be regarded as random or stochastic techniques, since they explore the conformational space in a non-deterministic fashion, arc genetic algorithms (GA) [137, 1381 simulation methods, such as molecular dynamics (MD) and Monte Carlo (MC) simulations 1139], as well as simulated annealing [140], All of those approaches and their application to generate ensembles of conformations arc discussed in Chapter II, Section 7.2 in the Handbook. 

A molecular dynamics simulation samples the phase space of a molecule (defined by the position of the atoms and their velocities) by integrating Newton s equations of motion. Because MD accounts for thermal motion, the molecules simulated may possess enough thermal energy to overcome potential barriers, which makes the technique suitable in principle for conformational analysis of especially large molecules. In the case of small molecules, other techniques such as systematic, random. Genetic Algorithm-based, or Monte Carlo searches may be better suited for effectively sampling conformational space. 

In a different context, conformational analysis is essential for the analysis of molecular dynamics simulations. As discussed in Chapter 3, the direct output of a molecular dynamics simulation is a set of confonnations ( snapshots ) that were saved along the trajectory. These conformations are subsequently analyzed in order to extract information about the system. However, if, during a long simulation, the molecule moves from one... 

Khan KM et al. (2005) A facile and improved synthesis of sildenafil (Viagra) analogs through solid support microwave irradiation possessing tyrosinase inhibitory potential, their conformational analysis and molecular dynamics simulation studies. Mol Divers 9(l-3) 15-26... 

Finally, Burkhard Luy, Andreas Frank and Horst Kessler discuss Conformational Analysis of Drugs by Nuclear Magnetic Resonance Spectroscopy . The determination and refinement of molecular conformations comprehends three main methods distance geometry (DG), molecular dynamics (MD) and simulated anneahng (SA). In principle, it is possible to exclusively make use of DG, MD or... 

Andre, S. Pei, Z. Siebert, H.-C. Ramstrom, O. Cabins, H.-J. Glycosyl-disulfides from dynamic combinatorial libraries as O-glycoside mimetics for plant and endogenous lectins Their reactivities in solid-phase and cell assays and conformational analysis by molecular dynamics simulations. Bioorg. Med. Chem. 2006,14, 6314-6326. 

A combination of the two techniques was shown to be a useful method for the determination of solution structures of weakly coupled dicopper(II) complexes (Fig. 9.4)[119]. The MM-EPR approach involves a conformational analysis of the dimeric structure, the simulation of the EPR spectrum with the geometric parameters resulting from the calculated structures and spin hamiltonian parameters derived from similar complexes, and the refinement of the structure by successive molecular mechanics calculation and EPR simulation cycles. This method was successfully tested with two dinuclear complexes with known X-ray structures and applied to the determination of a copper(II) dimer with unknown structure (Fig. 9.5 and Table 9.9)[119]. 

The conformational analysis of oligothiophenes by use of a combined molecular dynamics (MD)/NMR spectroscopic protocol has been carried out. A series of MD simulations were performed for 2-(2-thienyl)-3-hexylthiophene 173, 2,5-bis(3 -hexyl-2 -thienyl)thiophene 176, and 2,5-bis(4 -hexyl-2 -thienyl)-thiophene 177, with a new MM2 torsional parameter set developed earlier for unsubstituted and methyl-substituted 2,2 -bithiophene. 

---