Virtual Screening and Molecular Design Based on Hierarchical Qsar Technology

Кузьмин, В. Е.; Artemenko, Anatoly G.; Muratov, Eugene; Polischuk, Pavel G.; Ognichenko, L. N.; Liahovsky, Anatoly V.; Hromov, Alexander I.; Varlamova, Ekaterina V.

doi:10.1007/978-1-4020-9783-6_5

Cited by 24 publications

(19 citation statements)

References 62 publications

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“…In fact, fragmentation is an idea that inspired the Hammett equation, in which two molecular fragments are identified; one is a regular aromatic carboxylic acid framework, while the second is based on a series of its changing substituents. To give an analogy, Hansch's lipophilicity is constructed on a similar approach, and the Rekker hydrophobic fragmental approach [120] even more closely resembles the current fragmentation methods, 1D simplexes [121], i.e., the collections of any atomic combination, can be cite here as the deepest fragmentation concept, while the neural network procedure can be classified as a fuzzy 1D or 2D simplex identification [122,123]. The evolution of the early fragmental concepts is shown in Fig.…”

Section: From Early Fragmental Concepts In Chemistry and Drug Design mentioning

confidence: 99%

Privileged Structures - Dream or Reality: Preferential Organization of Azanaphthalene Scaffold

Polański

Kurczyk²,

Bąk³

et al. 2012

CMC

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The concept of privileged structures/substructures (PS) is the idea that certain structural features produce biological effects more often than others. The PS method can be seen as an offspring of fragonomics, which is based on recent experimental measurements of protein-ligand interactions. If PS prove to be true, then chemical motives that enrich biological activity can be used when designing new drugs. However, PS remain controversial because we cannot be sure whether the excess of active structures does not result from an abundance in chemical libraries. In this review, we will focus, in particular, on the preferential organization of azanaphthalene scaffolds (AN) in drugs and natural products (NP), which are preferred by Nature in evolution. We will show that knowledge discovery in molecular databases can reveal interesting time-trends profiles for important classes of potentially privileged scaffolds. The chemical library of AN is dominated by monoaza-compounds, among which quinoline appears to be the most frequently investigated scaffold; however; more sophisticated database mining seems to indicate different PS patterns within the AN scaffold family.

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Section: From Early Fragmental Concepts In Chemistry and Drug Design mentioning

confidence: 99%

Privileged Structures - Dream or Reality: Preferential Organization of Azanaphthalene Scaffold

Polański

Kurczyk²,

Bąk³

et al. 2012

CMC

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“…It should be noted that vertices 1 and 2 for C 32 , as well as vertices 7,8,9,10,13,14,43,44,45,46,49, 50 for C 78 are achiral (marked as Ø is following tables) because there are at least two topologically equivalent terminal vertices in respective simplexes (Fig. 8).…”

Section: Results: the Assessment Of Equivalence/nonequivalence Of Thementioning

confidence: 98%

“…In this case, IF reflects information about the distribution of the target property in space. Nowadays, IF theory was utilized as a powerful descriptive tool for "structure-property" tasks [3,4,[6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Efficacy of topological informational potentials for analysis of nonequivalent atoms in molecular graphs: the case of chiral fullerenes

et al. 2016

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In this study, the topological informational field was applied for the assessment of equivalence or nonequivalence of atoms and molecular fragments in structurally homogeneous chiral fullerenes. Two types of so-called topological informational potentials were calculated using noniterative heuristic method. Application of methods that allow estimating the nonequivalence of similar atoms could be a breakthrough for the description of highly homogenous structures. It was shown that method, which takes into account multiple paths in the molecular graph, is the most efficient. Results of equivalence/nonequivalence analysis allow to differentiate sources of molecule's chirality.

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“…Two types of cross validation can be used in QSAR analysis: leave-one-out and leave-group-out cross validation. The latter is a more severe method for model robustness estimation [50].…”

Section: Qsar Analysis Using Simplex Representation Of Molecular Strumentioning

confidence: 99%

Quantitative Structure-Property Relationship Analysis of Drugs’ Pharmacokinetics Within the Framework of Biopharmaceutics Classification System Using Simplex Representation of Molecular Structure

Golovenko

Borisyuk

Kulinskiy

et al. 2014

Challenges and Advances in Computational Chemistry and Physics

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The Biopharmaceutics Classification System (BCS) categorizes drugs into one of four biopharmaceutical classes according to their water solubility and membrane permeability characteristics and broadly allows the prediction of the rate-limiting step in the intestinal absorption process following oral administration. When combined with the in vitro dissolution characteristics of the drug product, the BCS takes into account three major factors: solubility, intestinal permeability, and dissolution rate, all of which govern the rate and extent of oral drug absorption from immediate-release (IR) solid oral-dosage forms. The concept of BCS provides a better understanding of the relationship between drug release from the product and the absorption process. This report reviews the current status of computational tools in predicting the base properties (aqueous solubility, and passive absorption) of the BCS and explores the application of the Simplex representation of molecular structure (SiRMS) QSAR approach in absorption (bioavailability) research. The main advantages of SiRMS are consideration of the different physico-chemical properties of atoms, high robustness, predictivity, and interpretability of developed models that creates good opportunities for molecular design. The reliability of developed QSAR models as predictive virtual screening tools and their utility for targeted drug design were validated by subsequent synthetic and biological experiments. The SiRMS approach was implemented as "HiT QSAR" software. In addition, we provide our perspective on the progress of research into an in silico equivalent to the BCS.

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Virtual Screening and Molecular Design Based on Hierarchical Qsar Technology

Cited by 24 publications

References 62 publications

Privileged Structures - Dream or Reality: Preferential Organization of Azanaphthalene Scaffold

Privileged Structures - Dream or Reality: Preferential Organization of Azanaphthalene Scaffold

Efficacy of topological informational potentials for analysis of nonequivalent atoms in molecular graphs: the case of chiral fullerenes

Quantitative Structure-Property Relationship Analysis of Drugs’ Pharmacokinetics Within the Framework of Biopharmaceutics Classification System Using Simplex Representation of Molecular Structure

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