Comparative Molecular

Before the comparative molecular field analysis (CoMFA), BCUT descriptors, 4D-QSAR, and HYBOT descriptors arc discussed in more detail, some further descriptors are listed briefly. 

After an alignment of a set of molecules known to bind to the same receptor a comparative molecular field analysis CoMFA) makes it possible to determine and visuahze molecular interaction regions involved in hgand-receptor binding [51]. Further on, statistical methods such as partial least squares regression PLS) are applied to search for a correlation between CoMFA descriptors and biological activity. The CoMFA descriptors have been one of the most widely used set of descriptors. However, their apex has been reached. 

Mosimann S, S Meleshko and M N G Jones 1995. A Critical Assessment of Comparative Molecular Modeling of Tertiary Structures of Proteins. Proteins Structure, Function and Genetics 23 301-317. 

Cramer R D III, D E Patterson and J D Bunce 1988, Comparative Molecular Field Analysis (CoMFA). Effect of Shape on Binding of Steroids to Carrier Proteins. Journal of the American Chemical Societ 110 5959-5967. 

Poso A, R Juvonen and J Gynther 1995. Comparative Molecular Field Analysis of Compounds wii CYP2A5 Binding Affinity. Quantitative Structure-Activity Relationships 14 507-511. 

The high sodium ion concentration results in facile crystallisation of the sodium salt. This process of salting out with common salt may be used for recrystallisation, but sodium benzenesulphonate (and salts of other acids of comparable molecular weight) is so very soluble in water that the solution must be almost saturated with sodium chloride and consequently the product is likely to be contaminated with it. In such a case a pure product may be obtained by crystallisation from, or Soxhlet extraction with, absolute alcohol the sul-phonate is slightly soluble but the inorganic salts are almost insoluble. Very small amounts of sulphones are formed as by-products, but since these are insoluble in water, they separate when the reaction mixture is poured into water ... 

S Mosimann, R Meleshko, MNG lames. A critical assessment of comparative molecular modeling of tertiary structures of proteins. Proteins 23 301-317, 1995. 

RD Cramer III, DE Patterson, JD Bunce. Comparative molecular field analysis (CoMFA). 1. Effect of shape on binding of steroids to carrier proteins. J Am Chem Soc 110 5959-5967, 1988. 

SJ Cho, A Tropsha. Cross-validated R2-guided region selection for comparative molecular held analysis A simple method to achieve consistent results. J Med Chem 38 1060-1066, 1995. 

SJ Cho, ML Garsia, J Bier, A Tropsha. Stracture-based alignment and comparative molecular held analysis of acetylcholinesterase inhibitors. J Med Chem 39(26) 5064-5071, 1996. 

Fig. 4-14. Similarity maps comparing molecular diversity between two couples of CSP.

Et2 All coinitiators and MeCl, MeBr and Mel solvents at various temperatures. The H20 /EtAiei2/n-pentane system was also briefly investigated. A large number of comparative molecular weight and conversion data were gathered. The effect of MeX on the polymerization was investigated in detail. In this section, conversion and initiator efficiency data will be discussed. 

Bis(oxazohnes) figands have been so widely used for the Diels-Alder reaction between N-2-alkenoyl-l,3-oxazolidine-2-one and cyclopentadiene that Lipkowitz and Pradhan developed a QSAR (quantitative structure-activity relationship) using Comparative Molecular Field Analysis (CoMFA) for a set of 23 copper-catalysts containing mainly bis(oxazoline) figands. The generated... 

To compare molecular theoretical and molecular dynamics results, we have chosen the same wall-particle potential but have used the 6 - oo fluid particle potential. Equation 14, Instead of the truncated 6-12 LJ potential. This Is done because the molecular theory Is developed In terms of attractive particles with hard sphere cores. The parameter fi n Equation 8 Is chosen so that the density of the bulk fluid In equilibrium with the pore fluid Is the same, n a = 0.5925, as that In the MD simulations. 

Unsubstituted Poly(meta-phenylene) is far more soluble than poly(para-phen-ylene) PPP1 of comparable molecular weight due to the angular structure of the meta-derivative. Poly(meta-phenylene) 48 can be prepared using the Yamamoto procedure [20] ca. 35% of the material formed is soluble in toluene. 

Asikainen A, Tarhanen J, Poso A, Pasanen M, Alhava E, Jnvonen RO. Predictive valne of comparative molecular field analysis modelling of naphthalene inhibition of human CYP2A6 and mouse CYP2A5 enzymes. Toxicol In Vitro 2003 17 449-55. 

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... 

CoMSIA (comparative molecular similarity index analysis) is a recent development from CoMFA and does not suffer from the alignment problem. It has been used to model hERG potassium channel inhibition by drugs [59] and the toxicity of phenylsulfonyl carboxylates [60], organophosphates [61], and polybrominated diphenyl ethers [62], with results comparable to those from CoMFA. 

Poso A, luvonen R, Gynther I. Comparative molecular field analysis of compounds with CYP2A5 binding affinity. Quant Struct-Act Relat 1995 14 507-11. 

Swaan PW, Szoka FC, Jr. and Oie S. Molecular modeling of the intestinal bile acid carrier a comparative molecular field analysis study. J Comput Aided Mol Des 1997 11 581-8. 

Eveiy bond has a characteristic length and strength. Example compares molecular hydrogen with molecular fluorine. 

Compare molecular size/weight characteristics of branched and linear species eluting at V in each chromatogram. Under the universal calibration formalism branched and linear components have the same hydrodynamic volume at V ... 

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