DARC/PELCO method

The DARC/PELCO method (Methode de perturbation d environnements limites concentriques ordonnes)" " " for predicting the properties of organic... 

Hall, L.H. and Kier, L.B. (1978a). A Comparative Analysis of Molecular Connectivity, Hansch, Free-Wilson and Darc-Pelco Methods in the SAR of Halogenated Phenols. Eur.J.MedChem.,... 

Mercier, C. and Dubois, J.-E. (1979). Comparison of Molecular Connectivity and DARC/ PELCO Methods Performance in Antimicrobial, Halogenated Phenol QSARs. Eur.J.Med. 

Internal structural variables derived from purely structural information groups, as in the Free-Wilson method (5), global connectivity indices (6), ordered sites, such as in the DARC/ PELCO method (1),... 

In the DARC/PELCO method (1), the structural variable makes use of graph theory. It is based on simultaneous representation of ail structures (15) whose structural modifications are to be correlated with variations in property and of the population containing these structures. The environment concept is used to describe each structure as an ordered chromatic graph. The principle of syn chronous generation of a structure and of the series which contains it, called hyperstructure is used to describe the population to be studied. This concept and this principle, when applied to an isofocal population, define a multidimensional variable characterizing the chemical structure. 

The DARC/PELCO method (1) estimates an average u orma-tion vector I im) through use of the topochramatic vectm TiE and information I associated with each experimental structure of a population P including m ratities. The equation is then ... 

In addition to the tool for searching an optimal Structure-Activity relationship, the DARC/PELCO method also has several tools with which to exploit results in Drug Design. These concern the interpretation of the relation, its predictive capability and experiment planning. 

In the DARC/PELCO method, the Topo-Information predictive capacity is measured by Preference PR (lb) including all the struc-tures of P nerated from the studied population P and which do not belong to it ... 

DARC/PELCO METHOD A TOPOLOGICAL TOOL FOR OSAR SEARCH AND ITS RELIABLE PREDICTIVE CAPABILITY... 

DARC/PELCO analysis, a topological method dealing with structural environments, was originally proposed, and then later refined and broadened, by Dubois [Dubois et ai, 1966 Dubois et ai, 1973a Dubois et al., 1973b Dubois et al., 1976 Dubois, 1976]. 

Duperray, B., Chastrette, M., Makabeth, M.C. and Pacheco, H. (1976b). Analyse de I Activite Bactericide de Populations d Alcools Aliphatiques et de 3-Naphtols suivant les Methodes de Hansch et Darc-Pelco Effet d Allongement de Chaine. EurJ.Med.Chem., 11, 433-437. 

Mercier, C., Mekenyan, O., Dubois, J.-E. and Bonchev, D. (1991). DARC/PELCO and OASIS Methods I. Methodological Comparison. Modeling Purine pKa and Antitumor Activity. Eur. 

In this paper, we detail the steps needed to obtain a SAR. Beyond the choice of an activity-representing variable, which is not discussed here. SAR search requires the choice of a structural variable weU-suited to prediction and the choice of a precise relationship search method. We show the impact of the DARC/PELCO choices in evaluating and optimizing prediction reliability. 

In the DARC/PELCO Structural method an internal variable pertaining to the ordered generation of an exhaustive topology is used. We show to what extent this variable combines some qualities of other structural variables, avoids some of their drawbacks and permits an approach to prediction reliability ... 

The topochromatic vectors constitute the basic structural variable used in the DARC/PELCO correlation search method. This variable can be modified by extending or diminishing the dimensions of the structure representation space S/HS. The space is modulated according to structural criteria or to criteria pertaining to the information evolving with respect to the structural modifications. 

The DARC/PELCO variable remains non ambiguous and exhaustive throughout the treatment and is explicit it makes it possible to retrieve, by a very simple procedure, the structure of the compound whose activity is predicted equal to a required value. Thus, like the structural variable used in the Free-Wilson method, the DARC/PELCO variable is capable of all types of prediction. 

Dubois, J.-E., Laurent, D., Bost, P., Chambaud, S. and Mercier, C. (1976) Systeme DARC. Methode DARC/PELCO. Strategies de Recherche de Correlations Appliquees a une Population d Adamantanamines Antigrippales. Eur. J. Med. Chem., 11, 225-236. 

The DARC-PELCO approach [418—423] is a simple application of a hyperstructure concept to the Free Wilson method while the approach may be appropriate for extremely large data sets, e.g. for the derivation of lipophilicity contributions from partition coefficients, it is usdess for most structure-activity analyses, due to the much too large number of variables (compare eqs. 199 and 200, chapter 8) [390, 391]. The results from Hansch, Free Wilson, and DARC-PELCO analyses have been compared with each other [421, 422, 424] no advantages of the latter approach could be seen. 

The method calls for a combination of the DARC system (Description, Acquisition, Retrieval and Computer-aided design) and the PELCO procedure (Perturbation of an Environment Limited Concentric and Ordered). 

The method is based on a combination of the DARC system (Description, Acquisition, Retrieval and Computer-aided design) and the PELCO (Perturbation of an Environment Limited Concentric and Ordered) procedure. Moreover, it accounts for the simultaneous representation of all the data set compounds and the population of the compounds structurally contained in them the data set compounds, which are those compounds for which a molecular property has been experimentally evaluated, generate an ordered multidimensional space that constitutes a —> hyperstructure. 

Dubois, J.-E., Laurent, D. and Aranda, A. (1973a) DARC system. XVI. Theory of topology-information. I. Method for the perturbation of ordered, concentric, limited environments (PELCO)./. Chim. Phys. Phys-Chim. Biol, 70, 1608-1615. 

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