A5057247289- Protein Structure and Dynamics
- Computational Drug Discovery Methods
- Receptor Mechanisms and Signaling
- Enzyme Structure and Function
- RNA and protein synthesis mechanisms
- Monoclonal and Polyclonal Antibodies Research
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Bioinformatics and Genomic Networks
- Neuropeptides and Animal Physiology
- Neuroscience and Neuropharmacology Research
- Lipid Membrane Structure and Behavior
- DNA and Nucleic Acid Chemistry
- Chemical Synthesis and Analysis
- Influenza Virus Research Studies
- Mass Spectrometry Techniques and Applications
- Bacteriophages and microbial interactions
- Analytical Chemistry and Chromatography
- Neuroinflammation and Neurodegeneration Mechanisms
- Genetics, Bioinformatics, and Biomedical Research
- Machine Learning in Bioinformatics
- Advanced Proteomics Techniques and Applications
- HER2/EGFR in Cancer Research
- Protein purification and stability
- Glycosylation and Glycoproteins Research
University of Coimbra
2016-2025
Centro de Neurociências e Biologia Celular
2015-2023
Center for Innovation
2022-2023
Utrecht University
2016-2019
Institut des Sciences Cognitives Marc Jeannerod
2015-2019
Biocant
2019
Universidade do Porto
2005-2015
Rede de Química e Tecnologia
2005-2015
San Antonio College
2011
Cornell University
2009-2010
Alanine scanning mutagenesis of protein-protein interfacial residues can be applied to a wide variety protein complexes understand the structural and energetic characteristics hot-spots. Binding free energies have been estimated with reasonable accuracy empirical methods, such as Molecular Mechanics/Poisson-Boltzmann surface area (MM-PBSA), more rigorous computational approaches like Free Energy Perturbation (FEP) Thermodynamic Integration (TI). The main objective this work is development an...
We present the performance of HADDOCK, our information-driven docking software, in second edition D3R Grand Challenge. In this blind experiment, participants were requested to predict structures and binding affinities complexes between Farnesoid X nuclear receptor 102 different ligands. The models obtained Stage1 with HADDOCK ligand-specific protocol show an average ligand RMSD 5.1 Å from crystal structure. Only 6/35 targets within 2.5 reference, which prompted us investigate limiting...
We present SpotOn, a web server to identify and classify interfacial residues as Hot-Spots (HS) Null-Spots (NS). SpotON implements robust algorithm with demonstrated accuracy of 0.95 sensitivity 0.98 on an independent test set. The predictor was developed using ensemble machine learning approach up-sampling the minor class. It trained 53 complexes various features, based both protein 3D structure sequence. SpotOn interface is freely available at: http://milou.science.uu.nl/services/SPOTON/ .
The attrition rate of drugs in clinical trials is generally quite high, with estimates suggesting that approximately 90% fail to make it through the process. identification unexpected toxicity issues during preclinical stages a significant factor contributing this high failure. These can have major impact on success drug and must be carefully considered throughout development late-stage rejections or withdrawals candidates significantly increase costs associated development, particularly...
Proteins containing PSD-95/Discs-large/ZO-1 homology (PDZ) domains play key roles in the assembly and regulation of cellular signaling pathways represent putative targets for new pharmacotherapeutics. Here we describe first small-molecule inhibitor (FSC231) PDZ domain protein interacting with C kinase 1 (PICK1) identified by a screening approximately 44,000 compounds fluorescent polarization assay. The bound PICK1 an affinity similar to that observed endogenous peptide ligands (K(i) 10.1...
Understanding protein-protein association and being able to determine the crucial residues responsible for their (hot-spots) is a key issue with huge practical applications such as rational drug design protein engineering. A variety of computational methods exist detect hot-spots residues, but development fast accurate quantitative alanine scanning mutagenesis (ASM) continues be crucial. Using four complexes, we have compared variation standard ASM protocol developed at our group, based on...
Abstract Background In cancer research, high-throughput screening technologies produce large amounts of multiomics data from different populations and cell types. However, analysis such encounters difficulties due to disease heterogeneity, further exacerbated by human biological complexity genomic variability. The specific profile as a (or, more realistically, set diseases) urges the development approaches that maximize effect while minimizing dosage drugs. Now is time redefine approach drug...
Understanding protein-protein interactions is a key challenge in biochemistry. In this work, we describe more accurate methodology to predict Hot-Spots (HS) interfaces from their native complex structure compared previous published Machine Learning (ML) techniques. Our model trained on large number of complexes and significantly larger different structural- evolutionary sequence-based features. particular, added interface size, type interaction between residues at the complex, types...
Due to the importance of hot-spots (HS) detection and efficiency computational methodologies, several HS detecting approaches have been developed. The current paper presents new models predict for protein-protein protein-nucleic acid interactions with better statistics compared ones currently reported in literature. These are based on solvent accessible surface area (SASA) genetic conservation features subjected simple Bayes networks (protein-protein systems) a more complex multi-objective...
Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2) is composed of four structural proteins and several accessory non-structural proteins. SARS-CoV-2's most abundant protein, Membrane (M) has a pivotal role both during viral infection cycle host interferon antagonism. This highly conserved thus an interesting suitable target for drug discovery. In this paper, we explain the nature M protein homodimer. To do so, developed applied detailed robust in silico workflow to predict dimeric...
High-density lipoprotein (HDL) nanoparticles promote endothelial cell (EC) function and suppress inflammation, but their utility in treating EC dysfunction has not been fully explored. Here, we describe a fusion protein named ApoA1-ApoM (A1M) consisting of apolipoprotein A1 (ApoA1), the principal structural HDL that forms lipid nanoparticles, ApoM, chaperone for bioactive sphingosine 1-phosphate (S1P). A1M HDL-like particles, binds to S1P, is signaling competent. Molecular dynamics...
Alanine-scanning mutagenesis of protein-protein interfacial residues is a very important process for rational drug design. In this study, we have used the improved MM-PBSA approach that combining molecular mechanics and continuum solvent permits one to calculate free energy differences through alanine mutation. To identify binding determinants complex formed between IgG1 (immunoglobulin-binding protein G) G, extended experimental scanning study both proteins and, therefore, all complex. As...
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...
Proteins and protein-based complexes are the basis of many key systems in nature have been subject intense research last decades, an attempt to acquire comprehensive knowledge reactions that take place nature. Computational Alanine Scanning Mutagenesis approaches extensively used study protein interfaces determination most important residues for complex formation, Hot-spots. However, as it is usually applied protein-protein interfaces, we tried modify apply protein-DNA which also crucial but...