Molecular mechanics bond polarization

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 treatment of electrostatics and dielectric effects in molecular mechanics calculations necessary for redox property calculations can be divided into two issues electronic polarization contributions to the dielectric response and reorientational polarization contributions to the dielectric response. Without reorientation, the electronic polarization contribution to e is 2 for the types of atoms found in biological systems. The reorientational contribution is due to the reorientation of polar groups by charges. In the protein, the reorientation is restricted by the bonding between the polar groups, whereas in water the reorientation is enhanced owing to cooperative effects of the freely rotating solvent molecules. 

Using molecular mechanics calculations to assess the three-dimensional shape of a molecule, various surface properties such as polarity and size can be calculated. The dynamic molecular surface properties can be determined from the (low energy) conformation(s) of the drug molecule obtained by molecular mechanics calculations of conformational preferences. The potential advantage of this method is that the calculated surface character-sitics determine numerous physicochemical properties of the molecules including lipophilicity, the energy of hydration and the hydrogen bond formation capacity [187-... 

Since the parameters used in molecular mechanics contain all of the electronic interaction information to cause a molecule to behave in the way that it does, proper parameters are important for accurate results. MM3(2000), with the included calculation for induced dipole interactions, should model more accurately the polarization of bonds in molecules. Since the polarization of a molecular bond does not abruptly stop at the end of the bond, induced polarization models the pull of electrons throughout the molecule. This changes the calculation of the molecular dipole moment, by including more polarization within the molecule and allowing the effects of polarization to take place in multiple bonds. This should increase the accuracy with which MM3(2000) can reproduce the structures and energies of large molecules where polarization plays a role in structural conformation. 

A second mechanism (the polarization mechanism) arises due to the polarization of the fully occupied (bonding) crystal orbitals formed by the eg. oxygen 2p. and Li 2s atomic orbitals in the presence of a magnetic field. A fully occupied crystal (or molecular) orbital in reality comprises one one-electron orbital occupied by a spin-up electron and a second one-... 

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