Extended atom: molecular mechanics

Many problems in force field investigations arise from the calculation of Coulomb interactions with fixed charges, thereby neglecting possible mutual polarization. With that obvious drawback in mind, Ulrich Sternberg developed the COSMOS (Computer Simulation of Molecular Structures) force field [30], which extends a classical molecular mechanics force field by serai-empirical charge calculation based on bond polarization theory [31, 32]. This approach has the advantage that the atomic charges depend on the three-dimensional structure of the molecule. Parts of the functional form of COSMOS were taken from the PIMM force field of Lindner et al., which combines self-consistent field theory for r-orbitals ( nr-SCF) with molecular mechanics [33, 34]. 

The rapid rise in computer speed over recent years has led to atom-based simulations of liquid crystals becoming an important new area of research. Molecular mechanics and Monte Carlo studies of isolated liquid crystal molecules are now routine. However, care must be taken to model properly the influence of a nematic mean field if information about molecular structure in a mesophase is required. The current state-of-the-art consists of studies of (in the order of) 100 molecules in the bulk, in contact with a surface, or in a bilayer in contact with a solvent. Current simulation times can extend to around 10 ns and are sufficient to observe the growth of mesophases from an isotropic liquid. The results from a number of studies look very promising, and a wealth of structural and dynamic data now exists for bulk phases, monolayers and bilayers. Continued development of force fields for liquid crystals will be particularly important in the next few years, and particular emphasis must be placed on the development of all-atom force fields that are able to reproduce liquid phase densities for small molecules. Without these it will be difficult to obtain accurate phase transition temperatures. It will also be necessary to extend atomistic models to several thousand molecules to remove major system size effects which are present in all current work. This will be greatly facilitated by modern parallel simulation methods that allow molecular dynamics simulations to be carried out in parallel on multi-processor systems [115]. 

The extended Electron Distribution (XED) force field was first described by Vinter [96]. This force field proposes a different electrostatic treatment of molecules to that found in classical molecular mechanics methods. In classical methods, charges are placed on atomic centers, whereas the XED force field explicitly represents electron anisotropy as an expansion of point charges around each atom. The author claims that it successfully reproduces experimental aromatic ji stacking. Later, others made similar observations [97]. This force field is now available in Cresset BioMoleculaf s software package [95]. Apaya et al. were the first to describe the applicability of electrostatic extrema values in drug design, on a set of PDE III inhibitors [98]. 

The exponential increase in computer power and the development of highly efficient algorithms has distinctly expanded the range of structures that can be treated on a first-principle level. Using parallel computers, AIMD simulations of systems with few hundred atoms can be performed nowadays. This range already starts to approach the one relevant in biochemistry. Indeed, some simulations of entire biomolecules in laboratory-realizable conditions (such as crystals or aqueous solutions) have been performed recently [25-28]. For most applications however, the systems are still too large to be treated fully at the AIMD level. By combining AIMD simulations with a classical MD force field in a mixed quantum mechanical/molecular mechanical fashion (Hybrid-AIMD) the effects of the protein environment can be explicitly taken into account and the system size can be extended. 

The investigation of the colored form of spiropyrans by theoretical calculations started at the dawn of studies on photochromic compounds. The pioneering studies of a benzothiazolinic spiropyran were published by Guglielmetti and coworkers, who investigated the different planar forms of the open-form stereoisomers by calculations of the atomic interaction energies,31 the extended Hiickel method,3133 the PPP method,32 and theCNDO/2 method.34 The results of molecular mechanical (MM) calculations on spiropyrans and spirooxazines were compared with the X-ray structures and used to explain H NMR data.35... 

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