Molecular interaction field -based

Sdabola, S., Alex, A., Higginson, P.D., Mitchell, J.C., Snowden, M.J. and Morao, I. (2005) Theoretical prediction of the enantiomeric excess in asymmetric catalysis. An alignment-independent molecular interaction field based approach. J. Org. Chem., 70, 9025-9027. 

Historically, ligand structure-based design has been the most widely used approach to the design of target-directed chemical libraries. Methods that start from hits or leads are among the most diverse, ranging from 2D substructure search and similarity-based techniques to analysis of 3D pharmacophores and molecular interaction fields (Fig. 15.2). 

Figure 15.2 Historical progress of ligand structure-based approaches from substructure search to analysis of 3-dimensional molecular interaction fields.

Fig. 1.3 A survey of molecular properties molecular interaction fields MEPs, molecular based on their interdependence and the electrostatic potentials PK,...

A, B and V are constant for a given solute (Eig. 12.4 shows the value of A, 0.78, for atenolol). This means that the balance between intermolecular forces varies with the system investigated as would be expected from a careful reading of Section 12.1.1.3. This can also be demonstrated by using a completely different approach to factorize log P, i.e. a computational method based on molecular interaction fields [10]. Volsurf descriptors [11] have been used to calculate log P of neutral species both in n-octanol-water and in alkane-water [10]. 

Fig. 14.5 Computation of VolSurf descriptors [155, 156] derived from GRID molecular interaction fields. Interactions of the example molecule with a water and dry probe at different contour levels are used to compute a vector of 72 volume-, size- and surface-based descriptors.

We have already presented [17,18] the SCF-Ml (Self Consistent Field for Molecular Interactions) method, based on the idea that BSSE can be avoided a priori provided the MOs of each fragment are expanded only using basis functions located on each subsystem. In the present work we propose a multiconfiguration extension (MCSCF-MI) of the same technique, particularly suited to deal with systems for which proton transfer processes must be considered. 

Ahlstrom, M.M., Ridderstrom, M., Luthman, K. and Zamora, I. (2005) Virtual screening and scaffold hopping based on GRID molecular interaction fields. fournal of Chemical Information and Modeling, 45, 1313-1323. 

Mannhold, R., Berellini, G., Carosati, E. and Benedetti, P. (2006) Use ofMlF-based VolSurf descriptors in physicochemical and pharmacokinetic studies, in Molecular Interaction Fields (ed. G. Crudani), Wiley-VCH, Weinheim,... 

The set of 51 benzamidine-based thrombin inhibitors was taken from the study of Sugano et al. (2000). Experimental rat everted sac permeabilities were expressed as log(ES A) values.2 The experimental permeability in this assay is expressed as ratio of outer (mucosal side) concentration of the drug and inner (serosal side) concentration after 1 h incubation of the everted sac of rat small intestine. All molecules were treated in their neutral form and converted into their 3D structures using CORINA (Sadowski et al. 1992). From GRID molecular interaction fields for water, dry, and carbonyl oxygen probes, a set of 72 VolSurf descriptors (Cruciani et al. 2000) was computed and analysed as described above. 

The absence of a precise shape description, based on the GRID molecular interaction fields, prompted the development of a new procedure, called PathFinder, that is described here. 

We have presented a netv procedure, called PathFinder, aimed at encoding the GRID molecular interaction fields into invariant shape-descriptors, suitable for similarity and complementarity issues. Shape similarity is the underlying foundation of ligand-based methods tvhile shape complementarity is the basis of many receptor-based designs. 

In - grid-based QSAR techniques, the energy value at each grid point p constitutes a molecular descriptor. For the selected -> molecular interaction fields (steric, hydrophobic, coulombic, etc.), the calculated value at each grid point p depends on the relative orientation of the compound with respect to the grid. As a consequence, the use of... 

These are QSAR techniques, sometimes also referred to as CoMFA-like approaches, based on descriptors defined as molecular interaction energy values representing - molecular interaction fields or, in other words, the interaction energy between a - probe and a target compound embedded in a grid. 

Based on a similar approach to that used to define - WHIM descriptors, G-WHIM descriptors [Todeschini et al, 1997a Todeschini and Gramatica, 1998] are global molecular descriptors of - molecular interaction fields. 

The stereoelectronic representation (or lattice representation) of a molecule is a molecular description related to those molecular properties arising from electron distribution - interaction of the molecule with probes characterizing the space surrounding them (e.g. - molecular interaction fields). This representation is typical of - grid-based QSAR techniques. Descriptors at this level can be considered 4D-descriptors, being characterized by a scalar field, i.e. a lattice of scalar numbers associated with the 3D - molecular geometry. 

A field-based shape descriptor derived from the representation of molecular body by molecular interaction fields and defined as ... 

Another approach is based on the combination of molecular interaction fields using the 3D-QSAR technique CoMFA and soft independent modeling of class analogy (SIMCA) [33], Predictions were made for h % ranges by using the data sets from Refs [19, 27], with about 60% correctly classified. 

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