Monte Carlo simulation conformational analysis

Molecular mechanics calculations are an attempt to understand the physical properties of molecular systems based upon an assumed knowledge of the way in which the energy of such systems varies as a function of the coordinates of the component atoms. While this term is most closely associated with the conformational energy analyses of small organic molecules pioneered by Allinger (1), in their more general applications molecular mechanics calculations include energy minimization studies, normal mode calculations, molecular dynamics (MD) and Monte Carlo simulations, reaction path analysis, and a number of related techniques (2). Molecular mechanics... 

Fig. 18.13 Three representative stable conformers (65a-65c) for daphnicyclidin l< (65) analyzed by Monte Carlo simulation followed by minimization and clustering analysis [50],...

Simulation is the modelling of a system with its dynamic processes to gain knowledge, which can be transferred into reality. The most important simulation methods in the field of conformational analysis are molecular dynamics (MD) and Monte Carlo simulations, as well as simulated annealing [56,57], All these approaches are based on extensive numerical calculations and transformations. Therefore, only a brief introduction to these methods and their application to conformational searches is given in the following. 

T. Weimar, B. Meyer, and T. Peters, / Biomol. NMR, 3, 399 (1993). Conformational Analysis of a-D-Fuc-(l-4)-p-D-GlcNAc-OMe. One-Dimensional Transient NOE Experiments and Metropolis Monte Carlo Simulations. 

Bremard C, Buntinx G, Ginestet G (1997) Vibrational studies and Monte Carlo simulations of the sorption of aromatic carbonyls in faujasitic zeolites. J Mol Struct 410 379-382 Breneman CM, Wiberg KB (1990) Determining atom-centered monopoles from molecular electrostatic potentials The need for high samphng density in formamide conformational analysis. J Comput Chem... 

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. 

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