scholarly journals Virtual Screening of Marine Natural Compounds by Means of Chemoinformatics and CDFT-Based Computational Peptidology

Marine Drugs ◽  
2020 ◽  
Vol 18 (9) ◽  
pp. 478
Author(s):  
Norma Flores-Holguín ◽  
Juan Frau ◽  
Daniel Glossman-Mitnik
Keyword(s):  
Virtual Screening ◽  
Density Functional ◽  
Computational Study ◽  
Molecular System ◽  
Chemical Reactivity ◽  
Conceptual Density Functional Theory ◽  
Qsar Studies ◽  
Biological Targets ◽  
Global And Local

This work presents the results of a computational study of the chemical reactivity and bioactivity properties of the members of the theopapuamides A-D family of marine peptides by making use of our proposed methodology named Computational Peptidology (CP) that has been successfully considered in previous studies of this kind of molecular system. CP allows for the determination of the global and local descriptors that come from Conceptual Density Functional Theory (CDFT) that can give an idea about the chemical reactivity properties of the marine natural products under study, which are expected to be related to their bioactivity. At the same time, the validity of the procedure based on the adoption of the KID (Koopmans In DFT) technique, as well as the MN12SX/Def2TZVP/H2O model chemistry is successfully verified. Together with several chemoinformatic tools that can be used to improve the process of virtual screening, some additional properties of these marine peptides are identified related to their ability to behave as useful drugs. With the further objective of analyzing their bioactivity, some useful parameters for future QSAR studies, their predicted biological targets, and the ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) parameters related to the theopapuamides A-D pharmacokinetics are also reported.

scholarly journals Virtual Screening of Marine Natural Compounds by Means of Chemoinformatics and CDFT-Based Computational Peptidology

2020 ◽  
Author(s):  
Norma Flores-Holguín ◽  
Juan Frau ◽  
Daniel Glossman-Mitnik
Keyword(s):  
Virtual Screening ◽  
Density Functional ◽  
Computational Study ◽  
Chemical Reactivity ◽  
Conceptual Density Functional Theory ◽  
Qsar Studies ◽  
Molecular Systems ◽  
Biological Targets ◽  
Global And Local

This work presents the results of a computational study of the chemical reactivity and bioactivity properties of the members of the Theopapuamides A-D family of marine peptides by making use of our own proposed methodology named Computational Peptidology (CP) that has been successfully considered in previous studies of this kind of molecular systems. CP allowed for the determination of the global and local descriptors that come from Conceptual Density Functional Theory (CDFT) that can give an idea of the chemical reactivity properties of the marine natural products under study which are already known to be related to their bioactivity. At the same time, the validity of the procedure based on the adoption of the KID (Koopmans in DFT) technique as well as the MN12SX/Def2TZVP/H2O model chemistry has been successfully verified. Together with several Chemoinformatic tools that can be used for the improvement of process of Virtual Screening, some additional properties of these marine peptides were identified related to their ability to behave as useful drugs. With the further object of analyzing their bioactivity some parameters of usefulness for future QSAR studies, their predicted biological targets and the the ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) parameters related to the Theopapuamides A-D pharmacokinetics are also reported.

scholarly journals In Silico Pharmacokinetics, ADMET Study and Conceptual DFT Analysis of Two Plant Cyclopeptides Isolated From Rosaceae as a Computational Peptidology Approach

2021 ◽  
Vol 9 ◽  
Author(s):  
Norma Flores-Holguín ◽  
Juan Frau ◽  
Daniel Glossman-Mitnik
Keyword(s):  
Density Functional Theory ◽  
Density Functional ◽  
Chemical Reactivity ◽  
Conceptual Density Functional Theory ◽  
Functional Theory ◽  
Local Descriptors ◽  
Molecular Systems ◽  
Biological Targets ◽  
Global And Local

This research presents the outcomes of a computational determination of the chemical reactivity and bioactivity properties of two plant cyclopeptides isolated from Rosaceae through the consideration of Computational Peptidology (CP), a protocol employed previously in the research of similar molecular systems. CP allows the prediction of the global and local descriptors that are the integral foundations of Conceptual Density Functional Theory (CDFT) and which could help in getting in the understanding of the chemical reactivity properties of the two plant cyclopeptides under study, hoping that they could be related to their bioactivity. The methodology based on the Koopmans in DFT (KID) approach and the MN12SX/Def2TZVP/H2O model chemistry has been successfully validated. Various Chemoinformatics tools have been used to improve the process of virtual screening, thus identifying some additional properties of these two plant cyclopeptides connected to their ability to behave as potentially useful drugs. With the further objective of analyzing their bioactivity, the CP protocol is complemented with the estimation of some useful parameters related to pharmacokinetics, their predicted biological targets, and the Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) parameters related to the bioavailability of the two plant cyclopeptides under study are also reported.

scholarly journals Calculation of the Global and Local Conceptual DFT Indices for the Prediction of the Chemical Reactivity Properties of Papuamides A–F Marine Drugs

Molecules ◽  
2019 ◽  
Vol 24 (18) ◽  
pp. 3312 ◽  
Author(s):  
Norma Flores-Holguín ◽  
Juan Frau ◽  
Daniel Glossman-Mitnik
Keyword(s):  
Density Functional Theory ◽  
Active Sites ◽  
Density Functional ◽  
Chemical Reactivity ◽  
Active Regions ◽  
Conceptual Density Functional Theory ◽  
Functional Theory ◽  
Reactivity Descriptors ◽  
Global And Local

A well-behaved model chemistry previously validated for the study of the chemical reactivity of peptides was considered for the calculation of the molecular properties and structures of the Papuamide family of marine peptides. A methodology based on Conceptual Density Functional Theory (CDFT) was chosen for the determination of the reactivity descriptors. The molecular active sites were associated with the active regions of the molecules related to the nucleophilic and electrophilic Parr functions. Finally, the drug-likenesses and the bioactivity scores for the Papuamide peptides were predicted through a homology methodology relating them with the calculated reactivity descriptors, while other properties such as the pKas were determined following a methodology developed by our group.

scholarly journals Conceptual DFT-based Computational Peptidology of Marine Natural Compounds: Discodermins A–H

2020 ◽  
Author(s):  
Norma Flores-Holguín ◽  
Juan Frau ◽  
Daniel Glossman-Mitnik
Keyword(s):  
Density Functional Theory ◽  
Active Sites ◽  
Density Functional ◽  
Homology Model ◽  
Conceptual Density Functional Theory ◽  
Functional Theory ◽  
Fukui Functions ◽  
Reactivity Descriptors ◽  
Qsar Studies ◽  
Biological Targets

A methodology based on the concepts that arise from Density Functional Theory named Conceptual Density Functional Theory (CDFT) was chosen for the calculation of some global and local reactivity descriptors of the Discodermins A-H family of marine peptides through the consideration of the KID (Koopmans in DFT) technique that was successfully used in previous studies of this kind of molecular systems. The determination of active sites of the studied molecules for different kind of reactivities was achieved by resorting to some CDFT-based descriptors like the Fukui functions as well as the Parr functions derived from Molecular Electron Density Theory (MEDT). A few properties identified with their ability to behave as a drug and the bioactivity of the peptides considered in this examination were acquired by depending on a homology model by studying the correlation with the known bioactivity of related molecules in their interaction with various biological receptors. With the further object of analyzing their bioactivity some parameters of usefulness for future QSAR studies, their predicted biological targets and the the ADME (Absorption, Distribution, Metabolism, and Excretion) parameters related to the Discodermins A-H pharmacokinetics are also reported.

scholarly journals Conceptual DFT-Based Computational Peptidology of Marine Natural Compounds: Discodermins A–H

Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4158
Author(s):  
Norma Flores-Holguín ◽  
Juan Frau ◽  
Daniel Glossman-Mitnik
Keyword(s):  
Density Functional Theory ◽  
Active Sites ◽  
Density Functional ◽  
Homology Model ◽  
Conceptual Density Functional Theory ◽  
Functional Theory ◽  
Fukui Functions ◽  
Reactivity Descriptors ◽  
Qsar Studies ◽  
Biological Targets

A methodology based on the concepts that arise from Density Functional Theory named Conceptual Density Functional Theory (CDFT) was chosen for the calculation of some global and local reactivity descriptors of the Discodermins A–H family of marine peptides through the consideration of the KID (Koopmans in DFT) technique that was successfully used in previous studies of this kind of molecular systems. The determination of active sites of the studied molecules for different kinds of reactivities was achieved by resorting to some CDFT-based descriptors like the Fukui functions as well as the Parr functions derived from Molecular Electron Density Theory (MEDT). A few properties identified with their ability to behave as a drug and the bioactivity of the peptides considered in this examination were acquired by depending on a homology model by studying the correlation with the known bioactivity of related molecules in their interaction with various biological receptors. With the further object of analyzing their bioactivity, some parameters of usefulness for future QSAR studies, their predicted biological targets, and the ADME (Absorption, Distribution, Metabolism, and Excretion) parameters related to the Discodermins A–H pharmacokinetics are also reported.

Computational peptidology approach to the study of the chemical reactivity and bioactivity properties of Aspergillipeptide D, a cyclopentapeptide of marine origin

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Norma Flores-Holguín ◽  
Juan Frau ◽  
Daniel Glossman-Mitnik
Keyword(s):  
Density Functional ◽  
Computational Study ◽  
Chemical Reactivity ◽  
Therapeutic Drug ◽  
Moderate Activity ◽  
Conceptual Density Functional Theory ◽  
Reactivity Descriptors ◽  
Chemical Reactivity Descriptors ◽  
Aspergillus Sp

AbstractAspergillipeptide D is a cyclic pentapeptide isolated from the marine gorgonian Melitodes squamata-derived fungus Aspergillus sp. SCSIO 41501 that it has been shown to present moderate activity against herpes virus simplex type 1 (HSV-1). Thus, this paper presents the results of a computational study of this cyclopentapeptide’s chemical reactivity and bioactivity properties using a CDFT-based computational peptidology (CDFT-CP) methodology, which is derived from combining chemical reactivity descriptors derived from Conceptual Density Functional Theory (CDFT) and some Cheminformatics tools which may be used. This results in an improvement of the virtual screening procedure by a similarity search allowing the identification and validation of the known ability of the peptide to act as a possible useful drug. This was followed by an examination of the drug’s bioactivity and pharmacokinetics indices in relation to the ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) characteristics. The findings provide further evidence of the MN12SX density functional’s superiority in proving the Janak and Ionization Energy theorems using the proposed KID approach. This has proven to be beneficial in accurately predicting CDFT reactivity characteristics, which aid in the understanding of chemical reactivity. The Computational Pharmacokinetics study revealed the potential ability of Aspergillipeptide D as a therapeutic drug through the interaction with different target receptors. The ADMET indices confirm this assertion through the absence of toxicity and good absorption and distribution properties.

scholarly journals A CDFT-Based Computational Peptidology (CDFT-CP) Study of the Chemical Reactivity and Bioactivity of the Marine-Derived Alternaramide Cyclopentadepsipeptide

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Norma Flores-Holguín ◽  
Juan Frau ◽  
Daniel Glossman-Mitnik
Keyword(s):  
Density Functional ◽  
Computational Study ◽  
Chemical Reactivity ◽  
Therapeutic Drug ◽  
Inhibitory Effects ◽  
Conceptual Density Functional Theory ◽  
Functional Theory ◽  
Reactivity Descriptors ◽  
Chemical Reactivity Descriptors ◽  
And Staphylococcus Aureus

Alternaramide is a cyclic pentadepsipeptide isolated from marine sources that has been shown to present weak antibiotic activity against Bacillus subtilis and Staphylococcus aureus as well as inhibitory effects on inflammatory mediator expressions. Thus, this work reports the results of a computational study of the chemical reactivity and bioactivity properties of this cyclopentadepsipeptide considering a CDFT-based computational peptidology (CDFT-CP) methodology that results from the combination of the chemical reactivity descriptors that arise from conceptual density functional theory (CDFT) together with some cheminformatics tools that can be used to estimate the associated physicochemical parameters, to improve the process of virtual screening through a similarity search, and to identify the ability of the peptide to behave as a potential useful drug, complemented with an analysis of its bioactivity and pharmacokinetics indices related to the ADMET (absorption, distribution, metabolism, excretion, and toxicity) features. The results represent a new confirmation of the superiority of the MN12SX density functional in the fulfilment of the Janak and ionization energy theorems through the proposed KID procedure. This has been useful for the accurate prediction of the CDFT reactivity descriptors that help in understanding the chemical reactivity. The computational pharmacokinetics study revealed the potential ability of alternaramide as a therapeutic drug by interacting with GPCR ligands and protease inhibitors. The ADMET indices confirm this assertion through the absence of toxicity and good absorption and distribution properties.

Computational Study of Tetrahedral Fullerenes Containing Fused Pentagon-Triples

2021 ◽  
Vol 21 (4) ◽  
pp. 2419-2426
Author(s):  
Csaba L. Nagy ◽  
Katalin Nagy
Keyword(s):  
Density Functional ◽  
Computational Study ◽  
Chemical Shifts ◽  
Point Group ◽  
Functional Theory ◽  
Global Strain ◽  
The Stability ◽  
Global And Local ◽  
Hybrid Density Functional ◽  
Electronic And Structural Properties

Fullerenes that violate the isolated pentagon rule are too reactive and were obtained only as endoor exohedral derivatives. Density functional theory using the B3LYP hybrid density functional was applied to investigate the electronic and structural properties of the ten smallest tetrahedral (Td or T point group) fullerenes containing four directly fused pentagon-triples. The influence of nitrogen doping and exohedral hydrogenation of the four reactive sites was also analyzed. Nucleus independent chemical shifts values computed using B3LYP/6-31G(d) are used as global and local aromaticity probe. The global strain energy is evaluated in terms of the pyramidalization (POAV) angle. The results show that the stability increases with the elimination of the energetically unfavorable strain.

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