CoMFA lattice

CoMFA lattice -> comparative molecular field analysis... 

CoMFA lattice grid-based QSAR techniques ( Comparative Molecular Field Analysis)... 

Because a typical CoMFA lattice contains at least a thousand grid points, if we want to calculate two types of field for 20 compounds, the total number of interaction energies exceeds 40,000. This large number of calculations is currently feasible only when potential energy functions are used. Typically Lennard-Jones (6-12) steric and Coulombic electrostatic fields, > " and sometimes hydrogen bond potential functions,are used. 

A widely used 3-D QSAR method that makes use of PLS is comparative molecular field analysis (CoMFA), in which a probe atom is used to calculate the steric and electronic fields at numerous points in a 3D lattice within which the molecules have been aligned. Poso et al. [56] used the technique to model the binding of coumarins to cytochrome P450 2A5, with similar results to those obtained by Bravi and Wikel [55]. Shi et al. [57] used it to model the estrogen receptor binding of a large diverse set of compounds, and Cavalli et al. [58] used it to develop a pharmacophore for hERG potassium... 

Dick Cramer provided insight and inspirahon that led to my interest in 3D QSAR methodology ]40] and was the impetus (the precursor of CoMFA was a lattice model [41] developed by Cramer and Milne at SKF) behind the development of CoMFA (Comparative Molecular Field Analysis) by Tripos [42], The success of CoMFA in... 

The numbers of partial least squares (PLS) components were higher in CoMSIA than in CoMFA. This difference probably resulted from the significantly higher number of lattice points showing steadily varying field values (e.g., inside the molecules). The optimal numbers of components were selected on the basis of lowest Spress. 

An important feature of conventional CoMFA routine is that it assumes equal sampling and a priori equal importance of all lattice points for PLS analysis, whereas the final CoMFAresult actually emphasizes the limited areas of three-dimensional space as important... 

As a logical consequence, these methods were introduced in QSAR analyses and a new discipline, 3D QSAR, was bom. The major breakthrough in this field was achieved by Cramer et al.f who in 1988 described the application of comparative molecular field analysis (CoMFA) for the evaluation of the binding properties of steroids to carrier proteins. This approach, for which interestingly a patent application was filed by Cramer and Wold, and assigned to the software company Tripos, was based primarily on the previous work of Wise et on a dynamic lattice-oriented molecular modeling system (DYLOMMS) dating... 

The methods applied in recent years by various groups to construct QSAR models for ART and analogues include docking calculations to heme [104, 105], CoMFA [106-109] and hologram QSAR [108] as well as the hypothetical active-site lattice (HASL) approach [107], self-organizing maps of the molecular electrostatic potential [110], quantum-similarity measures [111] and topological molecular connectivity descriptors [112]. 

The points need not be on a lattice, such as is used in CoMFA. The CoMSIA method places the points inside the union surface of the superimposed molecules. The properties are not interaction energies, but rather the similarity of the molecular field of the ligand at a particular point with that of a probe atom. For this purpose steric, electrostatic, hydrophobic, and hydrogen bond acceptor and donor properties are considered. In the Compass method, probe atoms are placed along 162 equally spaced rays 2A from the union surface of the molecules in their initial superposition. The properties for analysis are the distance from the surface of the molecule to each of the probe atoms. 

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