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Protein Structure and Protein-Ligand Interactions

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

Deadline for manuscript submissions: closed (31 January 2023) | Viewed by 2140

Special Issue Editors


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Guest Editor
Faculty of Chemistry, University of Opole, Opole, Poland
Interests: computational chemistry; DFT; QMMM; enzymes; peptides; non-standard amino acids; drug design

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Guest Editor
The Czech Academy of Sciences | AVCR · Institute of Organic Chemistry and Biochemistry, Prague, Czech Republic
Interests: biomolecular spectroscopy

Special Issue Information

Dear Colleagues,

The functions of proteins and peptides in living organisms are extensive. They are involved in the regulation of metabolism as enzymes, act as signal transducers and play an important role in structural support and DNA expression. They can function as both ligands (hormones or peptide drugs) and receptors. Dysfunctions of enzymes and receptors lead to multiple diseases; therefore, they are the prime targets of drugs. In order to gain knowledge of the processes in which proteins and peptides are involved, it is necessary to properly resolve their structure, understand the structure–activity relationship (SAR), study the ligand–target interactions, and properly model reaction mechanisms. There are still many challenges that scientists in this field must face in order to fully understand the role and activity of peptides and proteins. 

We cordially invite scientists working with peptides and proteins, both experimentalists and specialists in molecular modelling, to submit their work to our Special Issue titled “Protein Structure and Protein–Ligand Interactions”, and to share their findings and research results in this field.  

The aim of this Special Issue is to bring together original papers, reviews and short communications presenting the recent knowledge and advances in protein structure characterization and protein–ligand interaction studies.

Dr. Monika Staś
Dr. Jiří Kessler
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 submissions that pass pre-check are 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 2700 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.

Published Papers (1 paper)

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Research

17 pages, 4969 KiB  
Article
Personalized Treatment for Infantile Ascending Hereditary Spastic Paralysis Based on In Silico Strategies
by Matteo Rossi Sebastiano, Giuseppe Ermondi, Kai Sato, Asako Otomo, Shinji Hadano and Giulia Caron
Molecules 2022, 27(20), 7063; https://doi.org/10.3390/molecules27207063 - 19 Oct 2022
Viewed by 1854
Abstract
Infantile onset hereditary spastic paralysis (IAHSP) is a rare neurological disease diagnosed in less than 50 children worldwide. It is transmitted with a recessive pattern and originates from mutations of the ALS2 gene, encoding for the protein alsin and involved in differentiation and [...] Read more.
Infantile onset hereditary spastic paralysis (IAHSP) is a rare neurological disease diagnosed in less than 50 children worldwide. It is transmitted with a recessive pattern and originates from mutations of the ALS2 gene, encoding for the protein alsin and involved in differentiation and maintenance of the upper motoneuron. The exact pathogenic mechanisms of IAHSP and other neurodevelopmental diseases are still largely unknown. However, previous studies revealed that, in the cytosolic compartment, alsin is present as an active tetramer, first assembled from dimer pairs. The C-terminal VPS9 domain is a key interaction site for alsin dimerization. Here, we present an innovative drug discovery strategy, which identified a drug candidate to potentially treat a patient harboring two ALS2 mutations: one truncation at lysine 1457 (not considered) and the substitution of arginine 1611 with a tryptophan (R1611W) in the C-terminus VPS9. With a protein modeling approach, we obtained a R1611W mutant model and characterized the impact of the mutation on the stability and flexibility of VPS9. Furthermore, we showed how arginine 1611 is essential for alsin’s homo-dimerization and how, when mutated to tryptophan, it leads to an abnormal dimerization pattern, disrupting the formation of active tetramers. Finally, we performed a virtual screening, individuating an already therapy-approved compound (MK4) able to mask the mutant residue and re-establishing the alsin tetramers in HeLa cells. MK4 has now been approved for compassionate use. Full article
(This article belongs to the Special Issue Protein Structure and Protein-Ligand Interactions)
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