A5007295898- Receptor Mechanisms and Signaling
- Computational Drug Discovery Methods
- Neuropeptides and Animal Physiology
- Chemical Synthesis and Analysis
- Protein Structure and Dynamics
- Pharmacological Effects and Assays
- Protein Hydrolysis and Bioactive Peptides
- Analytical Chemistry and Chromatography
- Neuroscience and Neuropharmacology Research
- Monoclonal and Polyclonal Antibodies Research
- Insect Utilization and Effects
- Transgenic Plants and Applications
- Mass Spectrometry Techniques and Applications
- Ion channel regulation and function
- Lipid Membrane Structure and Behavior
- Steroid Chemistry and Biochemistry
- melanin and skin pigmentation
- Peptidase Inhibition and Analysis
- Cell Adhesion Molecules Research
- HIV Research and Treatment
- HIV/AIDS Research and Interventions
- Regulation of Appetite and Obesity
- Influenza Virus Research Studies
- HIV/AIDS drug development and treatment
- Enzyme Structure and Function
University of Coimbra
2017-2025
Centro de Neurociências e Biologia Celular
2019
Stargazin, a transmembrane AMPAR regulatory protein (TARP), plays crucial role in facilitating the transport of AMPA receptors to cell surface, stabilising their localisation at synapses and influencing gating properties. The primary objective this study was investigate effect V143L mutation stargazin, previously linked intellectual disability, on interaction between stargazin receptors. To achieve this, we conducted thorough examination eight distinct molecular dynamics simulations...
The adenosine A2A receptor (A2AR), a class A GPCR, is known player in neurological diseases, including Parkinson's disease and Alzheimer's disease, also implicated SARS-CoV-2 infection. Recent studies have revealed its oligomerization with metabotropic glutamate type 5 (mGlu5R), C G protein coupled (GPCR) that exists the homodimeric form. Simultaneous activation of both receptors synergistically enhances mGlu5R-mediated effects hippocampus. Despite their importance, molecular mechanisms...
Background: Selectively targeting dopamine receptors (DRs) has been a persistent challenge in the last years for development of new treatments to combat large variety diseases involving these receptors. Although, several drugs have successfully brought market, subtype-specific binding mode on molecular basis not fully elucidated. Methods: Homology modeling and dynamics were applied construct robust conformational models all receptor subtypes (D1-like D2-like). Fifteen structurally diverse...
Abstract Mutations linked to neurodevelopmental disorders, such as intellectual disability (ID), are frequently found in genes that encode for proteins of the excitatory synapse. Transmembrane AMPA receptor regulatory (TARPs) auxiliary regulate crucial aspects function. Here, we investigate a mutant form TARP family member stargazin, described an ID patient. Molecular dynamics analyses predicted ID-associated stargazin variant, V143L, weakens overall interface AMPAR:stargazin complex and...
G protein-coupled receptors (GPCRs) are known to dimerize, but the molecular and structural basis of GPCR dimers is not well understood. In this study, we developed a computational framework generate models symmetric asymmetric using different monomer activation states identified their most likely interfaces with details. We chose dopamine receptor D2 (D2R) homodimer as case study because its biological relevance availability information. Our results showed that transmembrane domains 4 5...
The increase in the available G protein-coupled receptor (GPCR) structures has been pivotal helping to understand their activation process. However, role of protonation–conformation coupling GPCR still needs be clarified. We studied protonation behavior highly conserved Asp2.50 residue five different class A GPCRs (active and inactive conformations) using a linear response approximation (LRA) pKa calculation protocol. observed consistent differences (1.3 pK units) for macroscopic values...
G-Protein coupled receptors (GPCRs) are involved in a myriad of pathways key for human physiology through the formation complexes with intracellular partners such as G-proteins and arrestins (Arrs). However, structural dynamical determinants these still largely unknown. Herein, we developed computational big-data pipeline that enables characterization GPCR no available structure. This was used to study well-known group catecholamine receptors, dopamine receptor (DXR) family its complexes,...
SARS-CoV-2 triggered a worldwide pandemic disease, COVID-19, for which an effective treatment has not yet been settled. Among the most promising targets to fight this disease is main protease (Mpro), extensively studied in last few months. There urgency developing computational protocols that can help us tackle these key viral proteins. Hence, we have put together robust and thorough pipeline of silico protein–ligand characterization methods address one biggest biological problems currently...
Background: Selectively targeting dopamine receptors has been a persistent challenge in the last years for development of new treatments to combat large variety diseases evolving these receptors. Although, several drugs have successfully brought market, subtype-specific binding mode on molecular basis not fully elucidated. Methods: Homology modeling and dynamics were applied construct robust conformational models all receptor subtypes (D1-like D2-like receptors). Fifteen structurally diverse...
This paper describes an exciting big data analysis compiled in a freely available database, which can be applied to characterize the coupling of different G-Protein coupled receptors (GPCRs) families with their intracellular partners. Opioid receptor (OR) family was used as case study order gain further insights into physiological properties these important drug targets, known associated opioid crisis, huge socio-economic issue directly related abuse. An extensive characterization all...
Due to the clinical importance of Dopamine D2-receptor (D2R) in several brain dysfunctions, utilization silico models for drug development is a growing field investigation. We provided transparent and reproducible pipeline creating valid D2R model small molecular docking studies. Furthermore, we suggested binding pocket endogenous ligand D2R, which was attained upon careful consideration available experimental data. Molecular studies with Dopamine, Quinpirole Raclopride allowed also better...
Ghrelin is a peptide secreted in the gastric fundus and acts hypophysis hippocampus through Class A G-protein Coupled Receptor (GPCR), GHS-R1a. GPCRs are characterized by seven transmembrane (TM) spanning α-helices, connected to three extracellular (ECL) intracellular loops (ICL). (1) Activation of this receptor involved variety functions from feeding growth hormone release promotion learning memory. Among GPCRs, GHS-R1a an unusual high constitutive activity, absence specific ligands. (2)...