Synthesizing Amino Acids Modified with Reactive Carbonyls in Silico to Assess Structural Effects Using Molecular Dynamics Simulations.

Protein carbonylation by reactive aldehydes derived from lipid peroxidation leads to cross-linking, oligomerization, and aggregation of proteins, causing intracellular damage, impaired cell functions, and, ultimately, cell death. It has been described in aging and several age-related chronic conditions. However, the basis of structural changes related to the loss of function in protein targets is still not well understood.

Molecular dynamics of structural effects of reactive carbonyl species derivate of lipid peroxidation on bovine serum albumin.

Background: Serum albumin is the most abundant protein in the Mammalia blood plasma at where plays a decisive role in the transport wide variety of hydrophobic ligands. BSA undergoes oxidative modifications like the carbonylation by the reactive carbonyl species (RCSs) 4-hydroxy-2-nonenal (HNE), 4 hydroxy-2-hexenal (HHE), malondialdehyde (MDA) and 4-oxo-2-nonenal (ONE), among others. The structural and functional changes induced by protein carbonylation have been associated with the advancement of neurodegenerative, cardiovascular, metabolic and cancer diseases.

Cysteine carbonylation with reactive carbonyl species from lipid peroxidation induce local structural changes on thioredoxin active site.

Protein oxidative modifications with reactive carbonyl species (RCS) is directly linked to metabolic processes in premature aging, cancer, neurodegenerative and infectious diseases. RCS as 4-Hydroxy-2-nonal (HNE), 4-Hydroxy-2-hexenal (HHE), 4-Oxo-2-nonenal (ONE) and Malondialdehyde (MDA) attack nucleophilic amino acids residues forming irreversible adducts with proteins as Thioredoxins (Trx). This is a class of small thiol oxide-reductases playing a key role in redox signaling and oxidative stress responses in mammals.

study for the identification of potential destabilizers between the spike protein of SARS-CoV-2 and human ACE-2.

The emergence of the new SARS-CoV-2 virus, which causes the disease known as COVID-19, has generated a pandemic that has plunged the world into a health crisis. The infection process is triggered by the direct binding of the receptor-binding domain (RBD) of the spike (S) protein of SARS-CoV-2 to the angiotensin-converting enzyme 2 (ACE2) of the host cell. In the present study, virtual screening techniques such as molecular docking, molecular dynamics, calculation of free energy using the GBSA method, prediction of drug similarity, pharmacokinetic, and toxicological properties of various ligands interacting with the RBD-ACE2 complex were applied.

Bioinformatic Analysis of Plus Gene Expression Related to Progression from Leukoplakia to Oral Squamous Cell Carcinoma.

Introduction: Leukoplakia is one of the most frequently found lesions in the oral cavity, with a probability of 17 to 24% of becoming malignant cells in a period of 30 years.

Objective: To identify differentially expressed gene profiles of leukoplakia and its progression to oral squamous cell carcinoma, essential for the discovery of new biomarkers to predict and prevent the presence of diseases in the oral cavity.

Methods: Initially, gene profiles of GSE85514 and GSE160042 from the Gene Expression Omnibus database were used.

AMBER parameters and topology data of 2-pentylpyrrole adduct of arginine with 4-hydroxy-2-nonenal.

The data described here supports a part of the research article "Effect of 4‑HNE Modification on ZU5-ANK Domain and the Formation of Their Complex with β‑Spectrin: A Molecular Dynamics Simulation Study" [1]. Dataset on Gaff force field parameters of AMBER is provided for the non-standard arginine resulting of reaction with 4-hydroxy-2-nonenal (4-HNE), the major secondary product of lipids peroxidation. Arg-HNE 2-pentilpyrrole adduct is part of the 4-hydroxyalkenals described in various physiopathological disorders related to increased oxidative stress.

Effect of 4-HNE Modification on ZU5-ANK Domain and the Formation of Their Complex with β-Spectrin: A Molecular Dynamics Simulation Study.

4-HNE-modified ankyrins have been described in diseases such as diabetes, renal failure, G6PD deficient, sickle cell trait, infected erythrocytes with different AB0 blood groups. However, effects at the atomic level of this carbonylation on structure and function of modified protein are not yet fully understood. We present a study based on molecular dynamics simulations of nine 4-HNE modified residues of the ZU5-ANK ankyrin domain with β-spectrin and their binding energy profiles.

Development and benchmark to obtain AMBER parameters dataset for non-standard amino acids modified with 4-hydroxy-2-nonenal.

The data described here support the research article "4-HNE carbonylation induces local conformational changes on bovine serum albumin and thioredoxin. A molecular dynamics study" (Alviz-Amador et al., 2018) .

4-HNE carbonylation induces local conformational changes on bovine serum albumin and thioredoxin. A molecular dynamics study.

4-hydroxy-2-nonenal (4-HNE) is the main end product of peroxidation in lipids, capable of introduce carbonyl groups to nucleophilic amino acids via Michael additions and alter protein function. It has been reported that 4-HNE protein carbonylation is associated with intracellular protein aggregation, the pathogenesis of neurodegenerative and metabolic diseases and yet it is unclear how the carbonylation affects the protein structure and dynamics at the atomic level. Here, we analysis the structural effects of 4-HNE modification through formation of Michael adducts of Cys-4HNE, His-4HNE and Lys-4HNE on Serum Albumin (BSA) and Thioredoxin (TRX).