Dataset Information

Computational Pharmacokinetics Report, ADMET Study and Conceptual DFT-Based Estimation of the Chemical Reactivity Properties of Marine Cyclopeptides.

ABSTRACT: Homophymines A-E and A1-E1 are bioactive natural cyclodepsipeptides with a complex molecular architecture. These molecules could have a potential use as antimicrobial, antiviral, and anticancer substances. We have carried out a computational study of the properties of this family of marine peptides using 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 cheminformatics tools. The latter can be used to estimate the associated physicochemical parameters and to improve the process of virtual screening through a similarity search. Using this approach, the ability of the peptides to behave as a potentially useful drugs can be investigated. An analysis of their bioactivity and pharmacokinetics indices related to the ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) features has also been carried out.

SUBMITTER: Flores-Holguin N

PROVIDER: S-EPMC8607802 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Computational Pharmacokinetics Report, ADMET Study and Conceptual DFT-Based Estimation of the Chemical Reactivity Properties of Marine Cyclopeptides.

Flores-Holguín Norma N Frau Juan J Glossman-Mitnik Daniel D

ChemistryOpen 20211101 11

Homophymines A-E and A1-E1 are bioactive natural cyclodepsipeptides with a complex molecular architecture. These molecules could have a potential use as antimicrobial, antiviral, and anticancer substances. We have carried out a computational study of the properties of this family of marine peptides using 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) ...[more]

PMID: 34806828

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Project description:Modeling the various properties of liquid water, particularly its reactivity, has been a longstanding challenge for simulation methods. Recently, ab initio simulations based on density functional theory (DFT) have come to the fore as tenable methods for calculating the properties and reactivity of water, with varying degrees of success for different exchange-correlation functionals. In particular, hybrid-GGA and meta-GGA functionals have been shown to reproduce many of the structural, dynamical, and energetic properties of water to a high degree of accuracy relative to their computational cost. Here, we show that the dual descriptor (DD) measure of nucleophilicity and electrophilicity, which is sometimes used to elucidate organic chemistry reaction mechanisms, can also be used to characterize the reactivity of DFT-simulated liquid water. The DD is especially apt for understanding the reactivity of excess electrons with water as its calculation explicitly involves adding and removing an excess electron from a reference system. We use the DD to explore the reactivity of water simulated using three different DFT functionals: the LDA functional (LDA), a hybrid-GGA functional (PBE0), and a hybrid meta-GGA functional (SCAN0). Using the DD, we show that the SCAN0 functional with the standard 25% Hartree-Fock exchange produces simulated liquid water with many regions that are far more reactive than either PBE0 or LDA. To understand the implications of these highly reactive regions, we then add a strong nucleophile in the form of an excess electron and find that although PBE0 and LDA predict stable hydrated electrons, the excess electron reacts nearly instantaneously with SCAN0 water via proton abstraction to form a hydrogen atom and hydroxide ion. We show that the DD provides the ability to not only predict whether or not liquid water will react with a hydrated electron but also which particular waters will be involved solely from analyzing pure water configurations generated with each functional. We rationalize this result in terms of the known trap-seeking behavior of injected hydrated electrons, which are able to find the most electronegative region in bulk water. These results highlight the utility of the dual descriptor as a fast and interpretable method for investigating condensed-phase reactivity with excess electrons.

Dataset Information

Computational Pharmacokinetics Report, ADMET Study and Conceptual DFT-Based Estimation of the Chemical Reactivity Properties of Marine Cyclopeptides.

Publications

Computational Pharmacokinetics Report, ADMET Study and Conceptual DFT-Based Estimation of the Chemical Reactivity Properties of Marine Cyclopeptides.

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