Exploring structure–activity data using the landscape paradigm

Guha, Rajarshi

doi:10.1002/wcms.1087

Cited by 33 publications

(33 citation statements)

References 48 publications

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“…These methods allow the qualitative, quantitative, and/or visual analysis of the SAR and each has its own advantages and disadvantages ( Table 1). Activity landscape methods have emerged as a distinct approach to rapidly navigate through the SAR of datasets [17,19]. It should be noted that a number of these methodologies are ligand-based only.…”

Section: Mining Sars With Almmentioning

confidence: 99%

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Activity landscape of DNA methyltransferase inhibitors bridges chemoinformatics with epigenetic drug discovery

Naveja

Medina-Franco

2015

Expert Opinion on Drug Discovery

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The increasing SAR information reported for DNMTi opens up avenues to implement activity landscape methods. Despite several activity landscape methods, such as SAS maps, being well established, these need further refinement. For instance, novel combinations of multiple representations, such as the addition of Z-values of similarity (fusion-Z), lead to more robust representations of consensus SAS maps. Density SAS maps improve the visualization of the SAR. A survey of activity cliffs (i.e., pairs of compounds with high structural similarity but high differences in potency) of DNMTi available in a public database suggest that it is feasible to develop predictive models for non-nucleoside DNMTi using approaches such as quantitative structure-activity relationships and that non-nucleoside DNMTi in ChEMBL can be used as query molecules in similarity-based virtual screening.

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Section: Mining Sars With Almmentioning

confidence: 99%

“…Similar to the SAS maps, defining a unique 'high' SALI value is not easy as it depends, among other factors, on the structural representation used to compute the structural similarity. The SALI metric has been applied in several studies [19,30] including analysis of SmARs [36].…”

Section: Sas Mapsmentioning

confidence: 99%

Activity landscape of DNA methyltransferase inhibitors bridges chemoinformatics with epigenetic drug discovery

Naveja

Medina-Franco

2015

Expert Opinion on Drug Discovery

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“…From the modelers' perspective, the principle of similar structures having similar activities [76] is a cornerstone of quantitative structure-activity relationship (QSAR) modeling [77] [78]. This information is transformed and encoded for lots of problems chemical, pharmacological and toxicological studies on the relationship between structure-activity, quantitative structure-activity and structure-property (SAR, QSAR and QSPR) [79]- [81]. Ferreira et al [82] studied artemisinin and 18 derivatives with antimalarial activity against W-2 strains of Plasmodium falciparum through quantum chemistry and multivariate analysis.…”

Section: Application Of Hartree-fock Methods Using Computational Toolsmentioning

confidence: 99%

Application of Hartree-Fock Method for Modeling of Bioactive Molecules Using SAR and QSPR

Santos¹,

Lobato²,

Braga³

et al. 2014

CMB

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The central importance of quantum chemistry is to obtain solutions of the Schrödinger equation for the accurate determination of the properties of atomic and molecular systems that occurred from the calculation of wave functions accurate for many diatomic and polyatomic molecules, using Self Consistent Field method (SCF). The application of quantum chemical methods in the study and planning of bioactive compounds has become a common practice nowadays. From the point of view of planning it is important to note, when it comes to the use of molecular modeling, a collective term that refers to methods and theoretical modeling and computational techniques to mimic the behavior of molecules, not intend to reach a bioactive molecule simply through the use of computer programs. The choice of method for energy minimization depends on factors related to the size of the molecule, parameters of availability, stored data and computational resources. Molecular models generated by the computer are the result of mathematical equations that estimate the positions and properties of the electrons and nuclei, the calculations exploit experimentally, the characteristics of a structure, providing a new perspective on the molecule. In this work we show that studies of

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“…Progress in the development and applications of activity landscape modeling has been reviewed recently by Bajorath et al . and Guha . Major aspects addressed by these methods include single target and multitarget activity landscapes .…”

Section: Activity Landscape Modelingmentioning

confidence: 99%

Activity Cliffs: Facts or Artifacts?

Medina-Franco

2013

Chem Biol Drug Des

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The fact that similar compounds may have very different properties has a large impact in several areas of chemistry. In drug discovery, almost every medicinal chemist working on lead optimization has faced unexpected large 'jumps' in activity due to small changes in structure, that is, activity cliffs. A number of computational approaches have been developed to detect and quantify activity cliffs and help to understand, and eventually predict, structure-activity relationships (SAR) in compound data sets. Although activity cliffs do exist, the identification and quantification of cliffs have to proceed with caution because one may identify 'false positive cliffs'. In addition to apparent cliffs due to inaccurate determinations of activity, computationally identified cliffs can be artifacts attributed to the molecular representation and quantitative definition of 'high' structural similarity. This paper brings together and discusses, in a brief and integrated manner, some of the major aspects that raise the question whether all the activity cliffs detected in compound data sets are facts or artifacts.

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Exploring structure–activity data using the landscape paradigm

Cited by 33 publications

References 48 publications

Activity landscape of DNA methyltransferase inhibitors bridges chemoinformatics with epigenetic drug discovery

Activity landscape of DNA methyltransferase inhibitors bridges chemoinformatics with epigenetic drug discovery

Application of Hartree-Fock Method for Modeling of Bioactive Molecules Using SAR and QSPR

Activity Cliffs: Facts or Artifacts?

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