Molecular Field Analysis CoMFA Approach

Comparative Molecular Field Analysis (CoMFA) Approach 

In the CoMFA method developed by Cramer et a molecule is described using electrostatic, steric, and, sometimes, hydrogen bonding fields calculated at the 

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Kim, K.H. and Martin, Y.C. (1991a). Direct Prediction of Dissociation Constants (pKg s) of Clo-nidine-Like Imidazolines, 2-Substituted Imidazoles, and l-Methyl-2-Substituted-Imidazoles from 3D Structures Using a Comparative Molecular Field Analysis (CoMFA) Approach. J.Med.Chem., 34,2056-2060. 

Kim, K.H. (1995c). Description of the Reversed-Phase High-Performance Liquid Chromatography (RP-HPLC) Capacity Factors and Octanol-Water Partition Coefficients of 2-Pyrazine and 2- ridine Analogues Directly from the Three-Dimensional Structures Using Comparative Molecular Field Analysis (CoMFA) Approach. Quant.Struct.-Act.Relat., 14, 8-18. 

RP-LC, multivariate analysis methods such as principle component analysis (PCA) and nonlinear mapping (NML), or comparative molecular field analysis (CoMFA) approaches and linear free energy-related (LFER) equations have been used to derive structure-retention relationships in chiral chromatography [16-18]. 

Kim, KH. (1992) 3D quantitative structure-activity relationships description of electronic effects directly from 3D structures using a grid comparative molecular field analysis (CoMFA) approach. Quant. Struct. -Act. Rdat., 11, 127-134. 

K. H. Kim, Quant. Struct.-Act. Relat., 11, 127 (1992). 3D-Quantitative Structure-Activity Relationships Description of Electronic Effects Direaly from 3D Structures Using a GRID-Comparative Molecular Field Analysis (CoMFA) Approach. 

All ligand-based molecular modeling studies focusing on agents able to bind the colchicine site were performed before the determination of the X-ray structure of the tubulin-colchicine complex (see below). Computational tools in this field were mainly used to derive three-dimensional QS ARs (through comparative molecular field analysis (CoMFA) and other original approaches), but CSI also constituted useful... 

Beside the descriptors, further attempts have been made to encode the 3D molecular structures with functions. Such are 3D-MoRSE code [54] spectrum-like representations [55] and radial distribution functions [56]. Also, experimentally determined infrared, mass, or NMR spectra can be taken to represent a molecule [57]. Another example is comparative molecular field analysis (CoMFA) where the molecular 3D structures are optimized together with the receptor [58]. This approach is often applied in drug design or in specific toxicology studies where the receptor is known. The field of molecular descriptors and molecular representations has exploded in the recent decades. Over 200 programs for calculating descriptors and different QSAR applications are listed on web page [59]. 

The most commonly used and possibly even classical method of 3D QSAR analysis is the Comparative Molecular Field Analysis (CoMFA) technique introduced by R. Cramer et al. in 1988. In almost 20 years since, it has seen substantial development and enhancement, as well as the creation of several related approaches. In general terms, it aims to identify the spatial regions around the molecule where certain local properties have a positive or negative effect on activity. 

An inexperienced user or sometimes even an avid practitioner of QSAR could be easily con-fiased by the multitude of methodologies and naming conventions used in QSAR studies. Two-dimensional (2D) and three-dimensional (3D) QSAR, variable selection and artificial neural network methods, comparative molecular field analysis (CoMFA), and binary QSAR present examples of various terms that may appear to describe totally independent approaches, which cannot be even compared to each other. In fact, any QSAR method can be generally defined as the application of mathematical and statistical methods to the problem of finding empirical relationships (QSARmod-els)of the form, D . D ), where... 

The seminal work of Corwin Hansch initiated the field of QSAR. Two-dimensional and three-dimensional QSAR methods (2-D QSAR and 3-D QSAR) have been widely applied to problems of biological interest. The latter approach has increased in popularity with the introduction of the comparative molecular field analysis (CoMFA) and commercial availability of similar methods. 

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