Surface descriptors

The MEP at the molecular surface has been used for many QSAR and QSPR applications. Quantum mechanically calculated MEPs are more detailed and accurate at the important areas of the surface than those derived from net atomic charges and are therefore usually preferable [Ij. However, any of the techniques based on MEPs calculated from net atomic charges can be used for full quantum mechanical calculations, and vice versa. The best-known descriptors based on the statistics of the MEP at the molecular surface are those introduced by Murray and Politzer [44]. These were originally formulated for DFT calculations using an isodensity surface. They have also been used very extensively with semi-empirical MO techniques and solvent-accessible surfaces [1, 2]. The charged polar surface area (CPSA) descriptors proposed by Stanton and Jurs [45] are also based on charges derived from semi-empirical MO calculations. 

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Zamora, I., Oprea, T., Cruciani, G., Pastor, M., and Ungell, A.-L. Surface descriptors for protein-ligand affinity prediction. /. Med. Chem. 2003, 46, 25-33. 

Chikhi R, Sael L, Kihara D (2010) Real-time ligand binding pocket database search using local surface descriptors. Proteins 78 2007-2028... 

QSAR methods can be divided into several categories dependent on the nature of descriptors chosen. In classical one-dimensional (ID) and two-dimensional (2D) QSAR analyses, scalar, indicator, or topological variables are examples of descriptors used to explain differences in the dependent variables. 3D-QSAR involves the usage of descriptors dependent on the configuration, conformation, and shape of the molecules under consideration. These descriptors can range from volume or surface descriptors to HOMO (highest occupied molecular orbital) and LUMO (lowest unoccupied molecular orbital) energy values obtained from quantum mechanics (QM) calculations. 

In section 6.1, we introduced the COSMO-RS polarization charge density, a, as a local average of the COSMO polarization charges over a region of ca. 0.5 A radius. In this section, we will introduce a list of other local surface descriptors. Some of them have already proved to be useful for improving the accuracy of COSMO-RS, while others are candidates for future improvements. Obviously the list given here only reflects the present state of our ideas, and it is open for good additional ideas. 

The first application of a surface-based pharmacophore correlation vector was reported by Stiefl and Baumann in 2003 [18] with the MaP (mapping property distributions of molecular surfaces) descriptor. They applied their MaP descriptor for QSAR applications. To our knowledge, an application of this descriptor to similarity searching has not been reported. 

Walls and Sternberg210 considered surface complementary for docking protein-protein complexes using a vdW-like soft core potential. The use of accessible surface area on binding and complexation has been discussed, for example, by Flower.205 Surface descriptors have been used to calculate solvation energies as part of the energetics of molecular association.144,188,211 Volume overlap was also used to quantify interactions of chemical compounds.201 The HINT exponential function and empirical atomic... 

Wess G (2002) How to escape the bottleneck of medicinal chemistry. Drug Disc Today 7 533-535 Zamora I, Oprea T, Cruciani G et al. (2003) Surface descriptors for protein-ligand affinity prediction. J Med Chem 46 25-33... 

The molecular matrix M and the Z-matrix are the natural starting points for the calculation of several 3D atomic and molecular descriptors, such as - quantum-chemical descriptors, molecular interaction fields, -> EVA descriptors, -> WHIM descriptors, - CoMMA descriptors, - Compass descriptors, and molecular surface descriptors. 

Goldman, B.B. and Wipke, W.T. (2000) Quadratic shape descriptors. 1. Rapid superposition of dissimilar molecules using geometrically invariant surface descriptors. J. Chem. Inf. Comput. Sci, 40, 644-658. 

The foregoing example uses geometry and connectivity to derive an equivalence between configurations. The same notion can be used for any other type of shape descriptor An equivalence between structures found along reaction paths has been derived in terms of surface descriptors.The result can be viewed as a form of the Hammond postulate expressed in terms of molecular shape, rather than differences of potential energy. 

Conformationally averaged surface descriptors, such as solvent-accessible areas, provide a realistic descriptor of the space spanned by a flexible molecule or a weakly bound complex. Simulations indicate correlations between the stability of a diastereomeric complex and its accessible dynamic... 

Shape Descriptors. 1. Rapid Superposition of Dissimilar Molecules Using Geometrically Invariant Surface Descriptors. 

Both the selection of classes of appropriate features, and how the bin distribution is accomplished, are the subjects of current research. One recent approach that holds promise is the expansion of 3D feature keys to include pharmacophoric or stereophoric features as surrogates for the macromolecular receptor site. Each of these features is comprised of a collection of three or four atomic environments (selected from a list including hydrogen-bond donors, acceptors, etc.) in association with interatomic distance ranges. Another theme is the introduction of a 3D surface descriptor as the basis for matching. 

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