Parameterized electrostatic potential method

There are several variations of this method. The PRDDO/M method is parameterized to reproduce electrostatic potentials. The PRDDO/M/FCP method uses frozen core potentials. PRDDO/M/NQ uses an approximation called not quite orthogonal orbitals in order to give efficient calculations on very large molecules. The results of these methods are fairly good overall, although bond lengths involving alkali metals tend to be somewhat in error. 

The final part is devoted to a survey of molecular properties of special interest to the medicinal chemist. The Theory of Atoms in Molecules by R. F.W. Bader et al., presented in Chapter 7, enables the quantitative use of chemical concepts, for example those of the functional group in organic chemistry or molecular similarity in medicinal chemistry, for prediction and understanding of chemical processes. This contribution also discusses possible applications of the theory to QSAR. Another important property that can be derived by use of QC calculations is the molecular electrostatic potential. J.S. Murray and P. Politzer describe the use of this property for description of noncovalent interactions between ligand and receptor, and the design of new compounds with specific features (Chapter 8). In Chapter 9, H.D. and M. Holtje describe the use of QC methods to parameterize force-field parameters, and applications to a pharmacophore search of enzyme inhibitors. The authors also show the use of QC methods for investigation of charge-transfer complexes. 

The PPD and shell models are nearly equivalent in this sense, because they model the electrostatic potential via static point charges and polarizable dipoles (of either zero or very small extent). Accuracy can be improved by extending the expansion to include polarizable quadrupoles or higher order terms.The added computational expense and difficulty in parameterizing these higher order methods has prevented them from being used widely. The accuracy of the ESP for dipole-based methods can also be improved by adding off-atom dipolar sites. 

It is evident that the computational results of the method critically depend on the quality of the parameterization and in particular on the point polarizabilities usually associated with atoms. The atomic polarizabilily parameters are generally obtained by fitting to either experimental or QM molecular polarizabilities or QM electrostatic potentials. The methods can also be divided into two groups additive and interactive models, depending on the level of interactions permitted between induced dipoles [20]. In the additive approach, polarizable sites are allowed to respond to an external electric field but not to permanent and induced multipoles on other sites within a molecule. In nonadditive, also called interactive, polarization models, instead, each of a molecule s polarizable sites is allowed to respond to an external electric field not only from other molecules but from other sites within the same molecule. Consequently, aU interacting sites polarize themselves. Under certain conditions, two inducible dipoles at short distances can cause a polarization... 

Electrostatic Potentials Chemical Applications Parameterization of Semiempirical MO Method. 

Density Functional Theory (DFT), Hartree-Fock (HF), and the Self-consistent Field Electrostatic Potentials Chemical Applications MNDO PM3 Semiempirical Methods Transition Metals SINDOl Parameterization and Application. 

Theoretical models include those based on classical (Newtonian) mechanical methods—force field methods known as molecular mechanical methods. These include MM2, MM3, Amber, Sybyl, UFF, and others described in the following paragraphs. These methods are based on Hook s law describing the parabolic potential for the stretching of a chemical bond, van der Waal s interactions, electrostatics, and other forces described more fully below. The combination assembled into the force field is parameterized based on fitting to experimental data. One can treat 1500-2500 atom systems by molecular mechanical methods. Only this method is treated in detail in this text. Other theoretical models are based on quantum mechanical methods. These include ... 

Three types of surface are in use for water simulations. The first consists of simple empirical models based on the LJ-C potential. There seems to be no purpose in continuing to develop and use such models as they give little, if any, new information. A second group attempts to improve the accuracy of the potential using semiempirical methods based on a comprehensive set of experimental data. These models allow for physical phenomena such as intramolecular relaxation, electrostatic induced terms, and many-body interactions, all of which are difficult to incorporate correctly in liquid water theories. There is room for much more work in these areas. The third group makes use of the most advanced ab initio methods to develop accurate potentials from first principles. Such calculations are now converging with parameterized surfaces based on accurate semiempirical models. Over the next few years it seems very likely that the continued application of the second and third approaches will result in a potential energy surface that achieves quantitative accuracy for water in the condensed phase. 

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