Molecular electrostatic potential surfaces MEPS

Figure 7-9. Oxacarbenium ion transition state, Immucillin-H and DADMe-Immucillin-H are shown. The nomenclature - DADMe is (4 -Deaza-l -Aza-2/-Deoxy-l/,N-9-Methylene)-Immucillin-H. On die right, the molecular electrostatic potential surfaces (MEP) for the oxacarbenium/hypoxanthine pair at die transition state, Immucillin-H and DADMe-Immucillin-H are shown. MEP were calculated at HF/STO-3G theory level for optimized geometry at BlLYP/6-31G(d) theory level and visualized by Molekel 4.0 at electron density of 0.008 electron/bohr...

To make an accurate FEP calculation, a good description of the system is required. This means that the parameters for the chosen force field must reproduce the dynamic behaviour of both species correctly. A realistic description of the environment, e.g. size of water box, and the treatment of the solute-solvent interaction energy is also required. The majority of the parameters can usually be taken from the standard atom types of a force field. The electrostatic description of the species at both ends of the perturbation is, however, the key to a good simulation of many systems. This is also the part that usually requires tailoring to the system of interest. Most force fields require atom centered charges obtained by fitting to the molecular electrostatic potential (MEP), usually over the van der Waals surface. Most authors in the studies discussed above used RHF/6-31G or higher methods to obtain the MEP. 

The above G(a) surface is a molecular electrostatic potential contour surface, MEPCO, for the contour value a. Note that in contrast to the case of electronic charge density contours, in a MEP analysis the function V(r), hence the threshold parameter a, can take both positive and negative values. 

A general method, proposed by Politzer and coworkers, to estimate physico-chemical properties depending on noncovalent interactions [Brinck et ai, 1993 Murray et al., 1993 Politzer etal., 1993 Murray et al., 1994]. This is based on molecular surface area in conjunction with some statistically-based quantities related to the - molecular electrostatic potential (MEP) at the - molecular surface. The electron isodensity contour surface [0.001 a.u. contour of Q(r)j is taken as the molecular surface model. 

Molecular structures may be considered at different levels, each containing certain types of information. The simplest representation is the empirical chemical formula, while a highly complex representation is a molecular electrostatic potential (MEP) representation on the van der Waals surface which includes both steric and electronic information. 

The properties p of the atoms i and j are considered for a particular topological distance d. Sjj is a Kronecker delta that represents additional constraints or conditions. The topological distance may also be replaced by the Euclidean distance, thus accounting for two- or three-dimensional arrangement of atoms. Three-dimensional spatial autocorrelation of physicochemical properties has been used to model the biological activity of compound classes [24]. In this case, a set of randomly distributed points is selected on the molecular surface, and all distances between the surface points are calculated and sorted into preset intervals. These points are used to calculate the spatial autocorrelation coefficient for particular molecular properties, such as the molecular electrostatic potential (MEP). The resulting descriptor is a condensed representation of the distribution of the property on the molecular surface. 

This is a model obtained by applying the —> GIPF approach (General Interaction Properties Function approach) proposed by Politzer and coworkers [Brinck, Murray et al., 1993 Murray, Brinckef al., 1993,1994] as general method to estimate —> physico-chemical properties in terms of —> molecular electrostatic potential (MEP) properties calculated at the —> molecular surface. The Politzer hydrophobic model was proposed as the following ... 

The simplest representation is the empirical chemical formula, while a molecular electrostatic potential (MEP) representation on the Van der Waals surface includes both steric and electronic information. Molecular properties can be divided into various categories (see Fig. 22.4). There are experimental and calculated properties. Intrinsic properties are directly related to the stracture without considering any interaction, such as molecular weight. Some properties are related to a substituent or fragment. When a compound interacts with a chemical or biological environment, we may define physicochemical properties, e.g. lipophilicity or ionization constants, biochemical properties, such as binding constants, and biological properties, such as activity or toxicity. 

Fig. 14.14. Molecular electrostatic potential (MEP) represents the electrostatic interaction of the positive unit diarge (probe) with molecule A. (a) the coordinate system and the vectors used in Eq. (14.34) (b) the equipotential surfaces V (r) for the water molecule (c) another way of showing the MEP one computes V/ ir) on the molecular surface (defined somehow). In more expensive books this is shown by coloring the surface using a certain convention color <-> MEP. Such information is usefiil, because the role of the MEP is to predict the site of attack of another molecule, which is able to approach the surface. MEP in a.u. means the interaction of a proton with the molecule. It is seen that the proton will attack the region of the oxygen atom, while an attack of CI would happen from the side of the hydrogens.

Clark and co-workers [493] have used DFT and MP2 computations along with natural bond orbital (NBO) analysis and features of the molecular electrostatic potential (MEP) surface (EPS) to explain why DMSO is such a good solvent. The MEP study revealed a number of strongly positive and negative regions that encourage intermolecular interactions, while the NBO analysis showed that the supposed S=0 double bond in (0113)280 is actually a coordinate covalent S+ 0 single bond. 

The normalized hydrogen-braid donor/acceptor constants can be obtained via (3) and (4) if experimental values for ct and P2 are available, but they can also be estimated from AMI calculated molecular electrostatic potential (MEP) surfaces (Emax min) ... 

ADMA = adjustable density matrix assembler AFDF = additive fiizzy density fragmentation GSTE = geometrical similarity as topological equivalence MEDLA = molecular electron density loge assembler MEP = molecular electrostatic potential RBSM = resolution-based similarity measures SGM = shape group methods VDWS = van der Waals surface ID, 2D, 3D = one, two, and three dimensions. 

Classical shape representations of molecules are based on assumed analogies between quantum mechanical molecules and macroscopic, classical objects. Since most of the mass of molecules is concentrated in the nuclei, it has appeared natural to place emphasis on nuclear arrangements, and the chemically more relevant shapes of electron densities have become the focus of molecular shapes analysis only recently. It is important to distinguish stereochemistry and molecular shape analysis. The term stereochemistry is commonly used for the 3D pattern of formal bonds, whereas molecular shape often refers to the shape of the fuzzy electron density cloud, or to simpler representations of large-scale molecular features, such as an a-helix or a -sheet of a protein. Several alternative shape representations are also used, such as fused sphere van der Waals (VDW) surfaces, Connolly surfaces, solvent accessibility surfaces, or molecular electrostatic potential (MEP) surfaces. 

CC = computational chemistry GUI = graphical user interface-, MEP = molecular electrostatic potential PC = personal computer, PES = potential energy surface QC = quantum chemistry. 

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