A5058688565- Protein Structure and Dynamics
- Mass Spectrometry Techniques and Applications
- Enzyme Structure and Function
- Computational Drug Discovery Methods
- Estrogen and related hormone effects
- Machine Learning in Materials Science
- Retinoids in leukemia and cellular processes
- Ubiquitin and proteasome pathways
- Growth Hormone and Insulin-like Growth Factors
- Natural Antidiabetic Agents Studies
- Neuroscience and Neuropharmacology Research
- Receptor Mechanisms and Signaling
- NF-κB Signaling Pathways
- Crystallography and molecular interactions
- Cytokine Signaling Pathways and Interactions
- Chemical Synthesis and Analysis
- PI3K/AKT/mTOR signaling in cancer
- Amino Acid Enzymes and Metabolism
- Bone health and osteoporosis research
- Bone Metabolism and Diseases
- Protein Interaction Studies and Fluorescence Analysis
- Chemistry and Stereochemistry Studies
- Pancreatic function and diabetes
- Cancer-related Molecular Pathways
- Signaling Pathways in Disease
University of Edinburgh
2018-2025
Hellenic Mediterranean University
2024
Academy of Athens
2021-2024
Algosystems (Greece)
2024
Many proteins recognise other via mechanisms that involve the folding of intrinsically disordered regions upon complex formation. Here we investigate how selectivity a drug-like small molecule arises from its modulation protein disorder-to-order transition. Binding compound AM-7209 has been reported to confer order an 'lid' region oncoprotein MDM2. Calorimetric measurements revealed truncation lid MDM2 increases apparent dissociation constant 250-fold. By contrast, little effect on binding...
Cyclophilins have been implicated in the pathophysiology of metabolic dysfunction-associated steatohepatitis (MASH). Pharmacological inhibition cyclophilin B isoform has potential to attenuate liver fibrosis MASH, but current inhibitors clinical trials lack selectivity. We previously reported novel tri-vector small-molecule inhibitor 1 that exhibited improved subtype selectivity by simultaneously engaging three pockets on surface cyclophilins. Here, we present structure–activity...
Relative binding free energy calculations in drug design are becoming a useful tool facilitating lead affinity optimization cost- and time-efficient manner. However, they have been limited by technical challenges such as the manual creation of large numbers input files to set up, run, analyze simulations. In this Application Note, we describe FEPrepare, novel web-based tool, which automates setup procedure for relative FEP dual-topology scheme NAMD, one major MD engines, using OPLS-AA force...
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Quercetin (QUE) is a well-known natural product that can exert beneficial properties on human health. However, due to its low solubility bioavailability limited. In the present study, we examine whether formulation with two cyclodextrins (CDs) may enhance pharmacological profile. Comparative interaction studies of quercetin 2-hydroxyl-propyl-β-cyclodextrin (2HP-β-CD) and 2,6-methylated cyclodextrin (2,6Me-β-CD) were performed using NMR spectroscopy, DFT calculations, in silico molecular...
The growth hormone-releasing hormone receptor (GHRHR) belongs to Class B1 of G protein-coupled receptors (GPCRs). GPCR peptides such, as (GHRH), have been proposed bind in a two-step model, where first the C-terminal region peptide interacts with extracellular domain and, subsequently, N-terminus seven transmembrane receptor, resulting activation. GHRHR has recently highlighted promising drug target toward several types cancer and shown be overexpressed prostate, breast, pancreatic, ovarian...
In the context of SAMPL6 challenges, series blinded predictions standard binding free energies were made with SOMD software for a dataset 27 host-guest systems featuring two octa-acids hosts (OA and TEMOA) cucurbituril ring (CB8) host. Three different models used, ModelA computes energy based on double annihilation technique; ModelB additionally takes into account long-range dispersion state corrections; ModelC introduces an empirical correction term derived from regression analysis SAMPL5...
Abstract Approaches for computing small molecule binding free energies based on molecular simulations are now regularly being employed by academic and industry practitioners to study receptor-ligand systems prioritize the synthesis of molecules ligand design. Given variety methods implementations available, it is natural ask how convergence rates final predictions these compare. In this study, we describe concept results SAMPL6 SAMPLing challenge, first challenge from SAMPL series focusing...
Osteoporosis, characterized by reduced bone density and increased fracture risk, affects over 200 million people worldwide, predominantly older adults postmenopausal women. The disruption of the balance between bone-forming osteoblasts bone-resorbing osteoclasts underlies osteoporosis pathophysiology. Standard treatment includes lifestyle modifications, calcium vitamin D supplementation specific drugs that either inhibit or stimulate osteoblasts. However, these treatments have limitations,...
<p>In the context of SAMPL6 challenges, series blinded predictions standard binding free energies were made with SOMD software for a dataset 27 host-guest systems featuring two octa-acids hosts (<i>OA </i>and <i>TEMOA) cucuribituril ring (<i>CB</i>8)<i> </i>host. Three different models used, <i>ModelA </i>computes energy based on double annihilation technique; <i>ModelB</i> additionally takes into account long-range...
ABSTRACT Beta-N-methylamino-L-alanine (BMAA) is a potential neurotoxic non-protein amino acid, which can reach the human body through food chain. When BMAA interacts with bicarbonate in body, carbamate adducts are produced, share high structural similarity neurotransmitter glutamate. It believed that and its L-carbamate bind glutamate binding site of ionotropic receptor 2 (GluR2). Chronic exposure to could cause neurological illness such as neurodegenerative diseases. However, mechanism...
Beta-N-methylamino-l-alanine (BMAA) is a potential neurotoxic nonprotein amino acid, which can reach the human body through food chain. When BMAA interacts with bicarbonate in body, carbamate adducts are produced, share high structural similarity neurotransmitter glutamate. It believed that and its l-carbamate bind glutamate binding site of ionotropic receptor 2 (GluR2). Chronic exposure to could cause neurological illness such as neurodegenerative diseases. However, mechanism action bound...
Modulating the function of Intrinsically Disordered Proteins (IDPs) with small molecules is considerable importance given crucial roles IDPs in pathophysiology numerous diseases. Reported binding affinities for ligands to diverse vary broadly and little known about detailed molecular mechanisms that underpin ligand efficacy. Molecular simulations IDP-ligand can help us understand mode action molecule inhibitors IDP function, but it still unclear how energies be modeled rigorously such a...
Modulating the function of Intrinsically Disordered Proteins (IDPs) with small molecules is considerable importance given crucial roles IDPs in pathophysiology numerous diseases. Reported binding affinities for ligands to diverse vary broadly, and little known about detailed molecular mechanisms that underpin ligand efficacy. Molecular simulations IDP can help us understand mode action molecule inhibitors function, but it still unclear how energies be modeled rigorously such a flexible class...
Background and Purpose: Growth hormone-releasing hormone (GHRH), a 44-residue neuropeptide produced in the hypothalamus, stimulates synthesis release of pituitary growth via binding to its cognate receptor, receptor (GHRHR). The GHRHR belongs Class B1 G protein-coupled receptors (GPCRs). GPCR peptides have been proposed bind two-step model, where firstly C-terminal region peptide interacts with extracellular domain subsequently, N-terminus seven transmembrane resulting activation. No...
A cancer-associated missense mutation in the nuclear receptor RXRα acts by allosteric mechanisms and impacts differently activity of its dimers, depending on dimerization partner.
In the context of SAMPL6 challenges, series blinded predictions standard binding free energies were made with SOMD software for a dataset 27 host-guest systems featuring two octa-acids hosts ( OA and TEMOA) cucuribituril ring CB 8) host. Three different models used, ModelA computes energy based on double annihilation technique; ModelB additionally takes into account long-range dispersion state corrections; ModelC introduces an empirical correction term derived from regression analysis SAMPL5...
Abstract Many proteins recognise other via mechanisms that involve the folding of intrinsically disordered regions upon complex formation. Here we investigate how selectivity a drug-like small molecule arises from its modulation protein disorder-to-order transition. Binding compound AM-7209 has been reported to confer order an ‘lid’ region oncoprotein MDM2. Calorimetric measurements revealed truncation lid MDM2 increases apparent dissociation constant 250-fold. By contrast, little effect on...
In the context of SAMPL6 challenges, series blinded predictions standard binding free energies were made with SOMD software for a dataset 27 host-guest systems featuring two octa-acids hosts ( OA and TEMOA) cucuribituril ring CB 8) host. Three different models used, ModelA computes energy based on double annihilation technique; ModelB additionally takes into account long-range dispersion state corrections; ModelC introduces an empirical correction term derived from regression analysis SAMPL5...