Molecules, flexible

While much of the development of methods has necessarily focussed on the simplest small, rigid molecules, the focus of recent crystal structure prediction studies has noticeably shifted to more complex molecular systems. This shift in the nature of targets for structure prediction somewhat reflects the feeling that, for small rigid molecules, current methods are already useful and, while they still require further refinement, there is a pressing need to extend the applicability of what has been learnt from rigid molecules to more general, flexible molecules. 

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Luckhurst G R 1985 Molecular field theories of nematics systems composed of uniaxial, biaxial or flexible molecules Nuclear Magnetic Resonance of Liquid Crystals ed J W Emsiey (Dordrecht Reidel)... 

Calculating the Potential of IVlean Force for Flexible Molecules... 

Judson R S, E P Jaeger and A M Treasurywala 1994. A Genetic Algorithm-Based Method for Dockin Flexible Molecules. Journal of Molecular Structure Theochem 114 191-206. 

Rather than calculate the etithaltty conti ibutioti of the torsional states individually, an empirical sum that is an integral multiple of 0.42 kcal mol per torsional degree of freedom is assigned to flexible molecules in MM3, Torsional motion of a methyl gntup is iK)t added k) a calculated because it is included in the... 

Example The distance between two ends of a large, flexible molecule can provide information about its structural properties or its interaction with solvent. Analysis of an angle can reveal a hinged motion in a macromolecule. 

Free rotation around each of the carbon-carbon bonds makes saturated fatty acids extremely flexible molecules. Owing to steric constraints, however, the fully extended conformation (Figure 8.1) is the most stable for saturated fatty acids. Nonetheless, the degree of stabilization is slight, and (as will be seen) saturated fatty acid chains adopt a variety of conformations. 

Consider the stereochemical relationships between these flexible stereoisomers. A flexible molecule is chiral only if each of its conformers is chiral and if no two conformers are mirror images. Which, if any, of the stereoisomers are chiral Rexible chiral molecules are enantiomers only if each of their conformers are mirror-images. Which, if any, of the stereoisomers are enantiomers and which are diastereomers ... 

Make a sketch of each decalin isomer, and label the orientation of the bridgehead hydrogens with respect to each ring (equatorial or axial). Build a plastic model of each isomer and determine its conformational flexibility (a flexible molecule can undergo a ring flip, but a locked molecule cannot). Is flexibility responsible for stabihty ... 

FIGURE 18.12 When the runny oil (top) is hydrogenated, it is converted into a solid fat (bottom). Hydrogen adds to the carbon-carbon double bonds, converting them into single bonds. The resulting more flexible molecules can pack together more closely and form a solid. 

The density of states (DOS) of lattice phonons has been calculated by lattice dynamical methods [111]. The vibrational DOS of orthorhombic Ss up to about 500 cm has been determined by neutron scattering [121] and calculated by MD simulations of a flexible molecule model [118,122]. 

In addition to the geometric, steric effects which flexibility directly modifles, all intramolecular electronic properties of a flexible molecule are also coupled to molecular structure. In a real material, such properties as molecular dipole. 

Ewing TJ, Makino S, Skillman AG, Kuntz ID. DOCK 4.0 search strategies for automated molecular docking of flexible molecule databases. J Comput Aided Mol Dei 2001 15 411-28. 

Modeling Pardaxin Channel. The remarkable switching of conformation in the presence of detergents or phospholipid vesicles (5) suggests that pardaxin is a very flexible molecule. This property helps to explain the apparent ability of pardaxin to insert into phospholipid bilayers. In addition, it is consistent with the suggestion that the deoxycholate-like aminoglycosteroids (5,7) present in the natural secretion from which pardaxin is purified (5) serve to stabilize its dissociated conformation. The question of the mechanism by which pardaxin assembles within membranes is important for understanding pore formation and its cytolytic activity (5). 

Very often, it is unknown which conformahon of a flexible molecule is needed. For example, in drug design, we hunt often for the so-called bioachve conformation, which is the molecule in its receptor-bound state. In this case, any other experimental structure of the isolated molecule - in vacuum, in soluhon or in crystal - can be the wrong choice. 

There has been considerable recent activity developing appropriate parameters to allow semi-empirical methods to describe a variety of biologically important systems, and their related properties, such as (i) enzyme reactivity, including both over- and through-barrier processes, (ii) conformations of flexible molecules such as carbohydrates, (iii) reactivity of metalloenzymes and (iv) the prediction of non-covalent interactions by addition of an empirical dispersive correction. In this review, we first outline our developing parameterisation strategy and then discuss progress that has been made in the areas outlined above. 

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