العلاقة الكمية للبنية بالتأثير

Quantitative structure-activity relationship (QSAR) (sometimes QSPR: quantitative structure-property relationship) is the process by which chemical structure is quantitatively correlated with a well defined process, such as biological activity or chemical reactivity. ‏ For example, biological activity can be expressed quantitatively as in the concentration of a substance required to give a certain biological response. Additionally, when physicochemical properties or structures are expressed by numbers, one can form a mathematical relationship, or quantitative structure-activity relationship, between the two. The mathematical expression can then be used to predict the biological response of other chemical structures.

QSAR's most general mathematical form is:

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SAR and the SAR paradox

The basic assumption for all molecule based hypotheses is that similar molecules have similar activities. This principle is also called Structure-Activity Relationship (SAR). The underlying problem is therefore how to define a small difference on a molecular level, since each kind of activity, e.g. reaction ability, biotransformation ability, solubility, target activity, and so on, might depend on another difference. A good example was given in the bioisosterism review of Patanie/LaVoie.[1]


In general, one is more interested in finding strong trends. Created hypotheses usually rely on a finite number of chemical data. Thus, the induction principle should be respected to avoid overfitted hypotheses and deriving overfitted and useless interpretations on structural/molecular data.

The SAR paradox refers to the fact that it is not the case that all similar molecules have similar activities.


Types

Fragment based (group contribution) It has been shown that the logP of compound can be determined by the sum of its fragments. Fragmentary logP values have been determined statistically. This method gives mixed results and is generally not trusted to have accuracy of more than ±0.1 units.[2]

Group or Fragment based QSAR aka GQSAR. GQSAR allows flexibility to study various molecular fragments of interest in relation to the variation in biological response. The molecular fragments could be substituents at various substitution sites in congeneric set of molecules or could be on the basis of pre-defined chemical rules in case of non-congeneric set. GQSAR also considers cross-terms fragment descriptors, which could be helpful in identification of key fragment interactions in determining variation of activity.<ref name="Ajmani_2008">{{cite journal | author = Ajmani S, Jadhav K, Kulkarni SA | title =

Group-Based QSAR (G-QSAR): Mitigating Interpretation Challenges in QSAR|journal=QSAR & Combinatorial Science | year = 2008 | month = November | volume = 28 | issue = 1 | pages = 36–51 |‏‎ ‎‏‎

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‏كيمياء دوائية ‏علاقة البنية بالتأثير ‏[[‏‎[[QSAR‏ ‏‎]]‎تصنيف:كيمياء صيدلية]] ‏

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  1. ^ Patani GA, LaVoie EJ (1996). "Bioisosterism: A Rational Approach in Drug Design". Chemical Reviews. 96 (8): 3147–3176. doi:10.1021/cr950066q. PMID 11848856. Unknown parameter |month= ignored (help)
  2. ^ Wildman SA, Crippen GM (1999). "‎ ‎ Prediction of physicochemical parameters by atomic contributions". J. Chem. Inf. Comput. Sci. 39 (5): 868–873. doi:10.1021/ci990307l. line feed character in |title= at position 2 (help)