Special Issue "Molecular Dynamics in Drug Design"

A special issue of Pharmaceuticals (ISSN 1424-8247).

Deadline for manuscript submissions: 30 June 2019

Special Issue Editor

Guest Editor
Prof. Roberta Galeazzi

Universita Politecnica delle Marche, Dipartimento di Scienze della Vita e dell'Ambiente, Ancona, Italy
Website | E-Mail
Interests: computer aided drug design; molecular dynamics simulation of membrane receptors and lipid bilayers; rational drug design; bacterial efflux pumps' inhibitors; computational design of novel nanovectors for drug delivery

Special Issue Information

Dear Colleagues,

Computer simulation techniques have become a major tool in the analysis of biomolecules’ properties and their behavior dynamics. In the last decades, their applicability has improved, and, among all tools available, molecular dynamics (MD) simulations have gained increasingly extensive usage for structure-based drug design research. Initially, MD was developed to investigate molecular models with a limited number of atoms, but today’s computers now enable investigations of large macromolecular systems with a simulation time reaching the microsecond range.

In this Special Issue of Pharmaceuticals, expert researchers are invited to present original papers that consider any advances in “Molecular Dynamics in Drug Design”. Special emphasis is placed on the development of new protocols for successful lead discovery, rational drug design, application cases in all field of medicinal and bioorganic chemistry aimed to new drug discovery. In addition, all papers concerning the applicability of MD to obtain better free-energy values for protein ligand recognition will be considered.

Other select topics are: membrane transporters and macromolecular targets in cancer, membrane transporters and antimicrobial resistance, membrane receptors structure and drug design, and lipid bilayer structure and function. Submissions of manuscripts from various fields of research are strongly encouraged.

Prof. Roberta Galeazzi
Guest Editor

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. Pharmaceuticals is an international peer-reviewed open access quarterly 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 850 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

  • Structure-based drug design
  • in silico screening
  • membrane receptor targeting drug design
  • protein motions
  • drug discovery
  • docking studies
  • sampling several protein conformations
  • free-energy prediction

Published Papers (2 papers)

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Research

Open AccessArticle Insights into the Molecular Mechanisms of Eg5 Inhibition by (+)-Morelloflavone
Pharmaceuticals 2019, 12(2), 58; https://doi.org/10.3390/ph12020058
Received: 13 March 2019 / Revised: 10 April 2019 / Accepted: 12 April 2019 / Published: 16 April 2019
PDF Full-text (4854 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
(+)-Morelloflavone (MF) is an antitumor biflavonoid that is found in the Garcinia species. Recently, we reported MF as a novel inhibitor of ATPase and microtubules-gliding activities of the kinesin spindle protein (Eg5) in vitro. Herein, we provide dynamical insights into the inhibitory mechanisms [...] Read more.
(+)-Morelloflavone (MF) is an antitumor biflavonoid that is found in the Garcinia species. Recently, we reported MF as a novel inhibitor of ATPase and microtubules-gliding activities of the kinesin spindle protein (Eg5) in vitro. Herein, we provide dynamical insights into the inhibitory mechanisms of MF against Eg5, which involves binding of the inhibitor to the loop5/α2/α3 allosteric pocket. Molecular dynamics simulations were carried out for 100 ns on eight complexes: Eg5-Adenosine diphosphate (Eg5-ADP), Eg5-ADP-S-trityl-l-cysteine (Eg5-ADP-STLC), Eg5-ADP-ispinesib, Eg5-ADP-MF, Eg5-Adenosine triphosphate (Eg5-ATP), Eg5-ATP-STLC, Eg5-ATP-ispinesib, and Eg5-ATP-MF complexes. Structural and energetic analyses were done using Umbrella sampling, Molecular Mechanics Poisson–Boltzmann Surface Area (MM/PBSA) method, GROMACS analysis toolkit, and virtual molecular dynamics (VMD) utilities. The results were compared with those of the known Eg5 inhibitors; ispinesib, and STLC. Our data strongly support a stable Eg5-MF complex, with significantly low binding energy and reduced flexibility of Eg5 in some regions, including loop5 and switch I. Furthermore, the loop5 Trp127 was trapped in a downward position to keep the allosteric pocket of Eg5 in the so-called “closed conformation”, comparable to observations for STLC. Altered structural conformations were also visible within various regions of Eg5, including switch I, switch II, α2/α3 helices, and the tubulin-binding region, indicating that MF might induce modifications in the Eg5 structure to compromise its ATP/ADP binding and conversion process as well as its interaction with microtubules. The described mechanisms are crucial for understanding Eg5 inhibition by MF. Full article
(This article belongs to the Special Issue Molecular Dynamics in Drug Design)
Figures

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Open AccessArticle Dissipative Particle Dynamics Investigation of the Transport of Salicylic Acid through a Simulated In Vitro Skin Permeation Model
Pharmaceuticals 2018, 11(4), 134; https://doi.org/10.3390/ph11040134
Received: 26 October 2018 / Revised: 24 November 2018 / Accepted: 29 November 2018 / Published: 5 December 2018
Cited by 2 | PDF Full-text (5899 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Permeation models are often used to determine diffusion properties of a drug through a membrane as it is released from a delivery system. In order to circumvent problematic in vivo studies, diffusion studies can be performed in vitro, using (semi-)synthetic membranes. In this [...] Read more.
Permeation models are often used to determine diffusion properties of a drug through a membrane as it is released from a delivery system. In order to circumvent problematic in vivo studies, diffusion studies can be performed in vitro, using (semi-)synthetic membranes. In this study salicylic acid permeation was studied, employing a nitrocellulose membrane. Both saturated and unsaturated salicylic acid solutions were studied. Additionally, the transport of salicylic acid through the nitrocellulose membrane was simulated by computational modelling. Experimental observations could be explained by the transport mechanism that was revealed by dissipative particle dynamics (DPD) simulations. The DPD model was developed with the aid of atomistic scale molecular dynamics (AA-MD). The choice of a suitable model membrane can therefore, be predicted by AA-MD and DPD simulations. Additionally, the difference in the magnitude of release from saturated and unsaturated salicylic acid and solutions could also be observed with DPD. Moreover, computational studies can reveal hidden variables such as membrane-permeant interaction that cannot be measured experimentally. A recommendation is made for the development of future model permeation membranes is to incorporate computational modelling to aid the choice of model. Full article
(This article belongs to the Special Issue Molecular Dynamics in Drug Design)
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Graphical abstract

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