Latest Frontiers and Applications in Target and Drug Discovery Field

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Drug Discovery, Development and Delivery".

Deadline for manuscript submissions: 30 September 2024 | Viewed by 297

Special Issue Editor


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Guest Editor
Department of Biotechnology, Chemistry, and Pharmacy, University of Siena, Siena, Italy
Interests: molecular modeling; molecular dynamics and docking simulation; structural biology; drug and target discovery

Special Issue Information

Dear Colleagues,

In recent decades, we have witnessed a worrying increase in disease outbreaks, and despite the enormous progress made by the scientific community, it is paramount to individualize pioneering drug and target discovery approaches for the biomedical field to improve patient life expectancy.

The proposed new methods, such as using large-scale omics data, the circular bioeconomy, precision medicine, and bioinformatics approaches, enable us to understand the molecular mechanisms of the onset of disorders and rare diseases, providing leading compounds to tackle such pathologies.

This research topic aims to shed light on the pivotal molecular mechanisms involved in disorders through innovative in vitro and in silico strategies.

As a Guest Editor of this Special Issue, I cordially invite scholars and experts to submit original research, reviews, and perspectives on the in vitro advancements and computational methods in this field.

Areas of interest include, but are not limited to, the following:

  • In vitro and bioinformatics methods for the prediction and validation of novel selective leading compounds and drug targets;
  • In vitro and bioinformatics approaches to rare diseases;
  • Target and drug discovery strategies within the circular bioeconomy

Dr. Alfonso Trezza
Guest Editor

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 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

  • molecular dynamics and docking simulation
  • molecular modeling
  • target and drug discovery
  • precision medicine
  • circular bioeconomy

Published Papers (1 paper)

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Research

13 pages, 971 KiB  
Article
Molecular and Evolution In Silico Studies Unlock the h4-HPPD C-Terminal Tail Gating Mechanism
by Alfonso Trezza, Ancuta Birgauan, Michela Geminiani, Anna Visibelli and Annalisa Santucci
Biomedicines 2024, 12(6), 1196; https://doi.org/10.3390/biomedicines12061196 - 28 May 2024
Viewed by 194
Abstract
The enzyme 4-hydroxyphenylpyruvate dioxygenase (4-HPPD) is involved in the catabolism of the amino acid tyrosine in organisms such as bacteria, plants, and animals. It catalyzes the conversion of 4-hydroxyphenylpyruvate to a homogenisate in the presence of molecular oxygen and Fe(II) as a cofactor. [...] Read more.
The enzyme 4-hydroxyphenylpyruvate dioxygenase (4-HPPD) is involved in the catabolism of the amino acid tyrosine in organisms such as bacteria, plants, and animals. It catalyzes the conversion of 4-hydroxyphenylpyruvate to a homogenisate in the presence of molecular oxygen and Fe(II) as a cofactor. This enzyme represents a key step in the biosynthesis of important compounds, and its activity deficiency leads to severe, rare autosomal recessive disorders, like tyrosinemia type III and hawkinsinuria, for which no cure is currently available. The 4-HPPD C-terminal tail plays a crucial role in the enzyme catalysis/gating mechanism, ensuring the integrity of the active site for catalysis through fine regulation of the C-terminal tail conformation. However, despite growing interest in the 4-HPPD catalytic mechanism and structure, the gating mechanism remains unclear. Furthermore, the absence of the whole 3D structure makes the bioinformatic approach the only possible study to define the enzyme structure/molecular mechanism. Here, wild-type 4-HPPD and its mutants were deeply dissected by applying a comprehensive bioinformatics/evolution study, and we showed for the first time the entire molecular mechanism and regulation of the enzyme gating process, proposing the full-length 3D structure of human 4-HPPD and two novel key residues involved in the 4-HPPD C-terminal tail conformational change. Full article
(This article belongs to the Special Issue Latest Frontiers and Applications in Target and Drug Discovery Field)
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