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Special Issue "Integrative Computational Strategies for Drug Screening"

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Computational and Theoretical Chemistry".

Deadline for manuscript submissions: closed (30 November 2020).

Special Issue Editors

Dr. Pilar Cossio
Website
Guest Editor
Max Planck Tandem Group, University of Antioquia, Colombia and Max Planck Institute of Biophysics, Frankfurt am Main, Germany.
Interests: molecular structure; computational and theoretical chemistry; molecular dynamics simulations, cryo-electron microscopy and single-molecule experiments
Dr. Claudio Cavasotto
Website
Guest Editor
Translational Medicine Research Institute (IIMT), CONICET-Universidad Austral, Pilar, Buenos Aires, Argentina, and Austral Institute for Applied Artificial Intelligence, Universidad Austral, Pilar, Buenos Aires, Argentina
Interests: computer-aided drug discovery; protein modelling; cheminformatics; machine learning in drug discovery
Dr. Mattia Sturlese
Website
Co-Guest Editor
Department of Pharmaceutical and Pharmacological Sciences, University of Padova (UNIPD),Padua, Italy
Interests: Molecular Dynamics simulations; computer-aided drug discovery; Cheminformatics; Drug Discovery by NMR

Special Issue Information

Dear Colleagues,

Computational methods for drug discovery have proven useful in the search for new therapeutic agents. There is a wide variety of strategies ranging from low cost pharmacophore-based methods to highly accurate techniques, for example, free energy perturbation or thermodynamic integration using molecular dynamics simulations. Recently, considerable progress has been made with protocols that combine different methods differing in computational costs and accuracy, allowing for an efficient compound screening. The purpose of this special edition Integrative Computational Strategies for Drug Screening” is to present the state-of-the-art methodologies for in silico drug discovery, covering the integration of the many  computational techniques -such as pharmacophore-based modeling, docking, molecular dynamics simulations, quantum mechanics-, and supplying the community with the most recent advances in the field.

Dr. Pilar Cossio
Dr. Claudio Cavasotto
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Drug discovery
  • Integrative methods
  • Funnel-like strategies
  • Pharmacophore
  • Docking
  • Molecular dynamics

Published Papers (3 papers)

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Research

Open AccessArticle
Molecular Modeling to Estimate the Diffusion Coefficients of Drugs and Other Small Molecules
Molecules 2020, 25(22), 5340; https://doi.org/10.3390/molecules25225340 - 16 Nov 2020
Abstract
Diffusion is a spontaneous process and one of the physicochemical phenomena responsible for molecular transport, the rate of which is governed mainly by the diffusion coefficient; however, few coefficients are available because the measurement of diffusion rates is not straightforward. The translational diffusion [...] Read more.
Diffusion is a spontaneous process and one of the physicochemical phenomena responsible for molecular transport, the rate of which is governed mainly by the diffusion coefficient; however, few coefficients are available because the measurement of diffusion rates is not straightforward. The translational diffusion coefficient is related by the Stokes–Einstein equation to the approximate radius of the diffusing molecule. Therefore, the stable conformations of small molecules were first calculated by molecular modeling. A simple radius rs and an effective radius re were then proposed and estimated using the stable conformers with the van der Waals radii of atoms. The diffusion coefficients were finally calculated with the Stokes–Einstein equation. The results showed that, for the molecules with strong hydration ability, the diffusion coefficients are best given by re and for other compounds, rs provided the best coefficients, with a reasonably small deviation of ~0.3 × 10−6 cm2/s from the experimental data. This demonstrates the effectiveness of the theoretical estimation approach, suggesting that diffusion coefficients have potential use as an additional molecular property in drug screening. Full article
(This article belongs to the Special Issue Integrative Computational Strategies for Drug Screening)
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Open AccessArticle
Computational Studies towards the Identification of Novel Rhodopsin-Binding Compounds as Chemical Chaperones for Misfolded Opsins
Molecules 2020, 25(21), 4904; https://doi.org/10.3390/molecules25214904 - 23 Oct 2020
Abstract
Accumulation of misfolded and mistrafficked rhodopsin on the endoplasmic reticulum of photoreceptor cells has a pivotal role in the pathogenesis of retinitis pigmentosa and a subset of Leber’s congenital amaurosis. One potential strategy to reduce rhodopsin misfolding and aggregation in these conditions is [...] Read more.
Accumulation of misfolded and mistrafficked rhodopsin on the endoplasmic reticulum of photoreceptor cells has a pivotal role in the pathogenesis of retinitis pigmentosa and a subset of Leber’s congenital amaurosis. One potential strategy to reduce rhodopsin misfolding and aggregation in these conditions is to use opsin-binding compounds as chemical chaperones for opsin. Such molecules have previously shown the ability to aid rhodopsin folding and proper trafficking to the outer cell membranes of photoreceptors. As means to identify novel chemical chaperones for rhodopsin, a structure-based virtual screening of commercially available drug-like compounds (300,000) was performed on the main binding site of the visual pigment chromophore, the 11-cis-retinal. The best 24 virtual hits were examined for their ability to compete for the chromophore-binding site of opsin. Among these, four small molecules demonstrated the ability to reduce the rate constant for the formation of the 9-cis-retinal-rhodopsin complex, while five molecules surprisingly enhanced the formation of this complex. Compound 7, 13, 20 and 23 showed a weak but detectable increase in the trafficking of the P23H mutant, widely used as a model for both retinitis pigmentosa and Leber’s congenital amaurosis, from the ER to the cell membrane. The compounds did not show any relevant cytotoxicity in two different human cell lines, with the only exception of 13. Based on the structures of these active compounds, a series of in silico studies gave important insights on the potential structural features required for a molecule to act either as chemical chaperone or as stabiliser of the 11-cis-retinal-rhodopsin complex. Thus, this study revealed a series of small molecules that represent a solid foundation for the future development of novel therapeutics against these severe inherited blinding diseases. Full article
(This article belongs to the Special Issue Integrative Computational Strategies for Drug Screening)
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Open AccessArticle
Drug Repurposing for Candidate SARS-CoV-2 Main Protease Inhibitors by a Novel In Silico Method
Molecules 2020, 25(17), 3830; https://doi.org/10.3390/molecules25173830 - 23 Aug 2020
Cited by 2
Abstract
The SARS-CoV-2 outbreak caused an unprecedented global public health threat, having a high transmission rate with currently no drugs or vaccines approved. An alternative powerful additional approach to counteract COVID-19 is in silico drug repurposing. The SARS-CoV-2 main protease is essential for viral [...] Read more.
The SARS-CoV-2 outbreak caused an unprecedented global public health threat, having a high transmission rate with currently no drugs or vaccines approved. An alternative powerful additional approach to counteract COVID-19 is in silico drug repurposing. The SARS-CoV-2 main protease is essential for viral replication and an attractive drug target. In this study, we used the virtual screening protocol with both long-range and short-range interactions to select candidate SARS-CoV-2 main protease inhibitors. First, the Informational spectrum method applied for small molecules was used for searching the Drugbank database and further followed by molecular docking. After in silico screening of drug space, we identified 57 drugs as potential SARS-CoV-2 main protease inhibitors that we propose for further experimental testing. Full article
(This article belongs to the Special Issue Integrative Computational Strategies for Drug Screening)
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