A5056460983- Computational Drug Discovery Methods
- Protein Structure and Dynamics
- Enzyme Catalysis and Immobilization
- Enzyme Structure and Function
- Carbohydrate Chemistry and Synthesis
- Microbial Metabolic Engineering and Bioproduction
- Enzyme Production and Characterization
- Glycosylation and Glycoproteins Research
- Microbial Natural Products and Biosynthesis
- Antibiotics Pharmacokinetics and Efficacy
- Protein Hydrolysis and Bioactive Peptides
- Antibiotic Resistance in Bacteria
- Amino Acid Enzymes and Metabolism
- Escherichia coli research studies
- Alzheimer's disease research and treatments
- Biochemical and Molecular Research
- Technology in Education and Healthcare
- Machine Learning in Materials Science
- Mosquito-borne diseases and control
- Receptor Mechanisms and Signaling
- Essential Oils and Antimicrobial Activity
- Microtubule and mitosis dynamics
- HIV Research and Treatment
- Cell Image Analysis Techniques
- Malaria Research and Control
GlaxoSmithKline (France)
2021-2022
GlaxoSmithKline (Spain)
2018-2021
Universidad de Alcalá
2011-2019
Roche (Switzerland)
2016-2019
GlaxoSmithKline (Netherlands)
2019
GlaxoSmithKline (United Kingdom)
2019
Departamento de Salud
2017
Universidad Autónoma de Madrid
2011-2015
University of London
2009-2015
Centro de Biología Molecular Severo Ochoa
2011-2015
Snail1 (Snail) and Snail2 (Slug) are transcription factors that share a similar DNA binding structure of four five C2H2 zinc finger motifs (ZF), respectively. Both bind specifically to subset E-box (E2-box: CAGGTG/CACCTG) in target promoters like the E-cadherin promoter key mediators epithelial-to-mesenchymal transition (EMT). However, there differences biological actions, affinities promoter, genes Snail2, although molecular bases presently unknown. In particular, role each ZF E-boxes EMT...
Spread of parasite resistance to artemisinin threatens current frontline antimalarial therapies, highlighting the need for new drugs with alternative modes action. Since only 0.2-1% asexual parasites differentiate into sexual, transmission-competent forms, targeting this natural bottleneck provides a tangible route interrupt disease transmission and mitigate selection. Here we present high-throughput screen gametogenesis against ~70,000 compound diversity library, identifying seventeen...
An ultrafast and accurate scoring function for protein-protein docking is presented. It includes (1) a molecular mechanics (MM) part based on 12-6 Lennard-Jones potential; (2) an electrostatic component implicit solvent model (ISM) with individual desolvation penalties each partner in the complex plus hydrogen bonding term; (3) surface area (SA) contribution to account loss of water contacts upon formation. The accuracy performance function, termed MM-ISMSA, have been assessed by comparing...
Chagas' disease, caused by the protozoan parasite Trypanosoma cruzi, is a potentially life-threatening condition that has become global issue. Current treatment limited to two medicines require prolonged dosing and are associated with multiple side effects, which often lead discontinuation failure. One way address these shortcomings through target-based drug discovery on validated T. cruzi protein targets. such target proteasome, plays crucial role in degradation turnover chymotrypsin-,...
Room temperature ionic liquids (ILs) can affect enzyme activity in some enzyme-catalyzed reactions, however the effects of these cosolvents on enzymes are not clearly understood. Using β-galactosidase from Thermus thermophilus HB27 (TTP0042), we found an important change classical regioselectivity transglycosylation reaction with this enzyme. The increases N-acetyl-D-lactosamine synthesis (Galβ[1→4]GlcNAc) when RTILs used instead traditional self-condensated products. To understand possible...
Essential oils (EOs) are vastly used as natural antibiotics in Complementary and Alternative Medicine (CAM). Their intrinsic chemical variability synergisms/antagonisms between its components make difficult to ensure consistent effects through different batches. Our aim is evaluate the use of artificial neural networks (ANNs) for prediction their antimicrobial activity. Methods. The composition activity 49 EOs, extracts, and/or fractions was extracted from NCCLS compliant works. fast (FANN)...
The binding of epothilones to dimeric tubulin and microtubules has been studied by means biochemical NMR techniques. We have determined the constants epothilone A (EpoA) B (EpoB) tubulin, which are 4 orders magnitude lower than those for microtubules, we elucidated conformation epitopes EpoA EpoB when bound dimers in solution. is similar that found X-ray crystallographic techniques Tubulin/RB3/TTL complex; it markedly different from reported zinc-induced sheets obtained electron...
The genome of the lactic acid bacterium Lactobacillus plantarum WCFS1 reveals presence a rich repertoire esterases and lipases highlighting their important role in cellular metabolism. Among them is carboxylesterase LpEst1 bacterial enzyme related to mammalian hormone-sensitive lipase, which known play central energy homeostasis. In this study, crystal structure has been determined at 2.05 Å resolution; it exhibits an αβ-hydrolase fold, consisting β-sheet surrounded by α-helices, endowed...
Abstract The human protease family HtrA is responsible for preventing protein misfolding and mislocalization, a key player in several cellular processes. Among these, HtrA1 implicated cancers, cerebrovascular disease age-related macular degeneration. Currently, activation not fully characterized relevant drug-targeting this protease. Our work provides mechanistic step-by-step description of regulation. We report that the trimer regulated by an allosteric mechanism which monomers relay signal...
Water molecules in protein binding sites play essential roles biological processes. The popular 3D-RISM prediction method can calculate the solvent density distribution within minutes, but is difficult to convert it into explicit water molecules.We present GAsol, a tool that capable of finding network best fits particular fast and accurate manner outperforms other available tools by globally optimal solution thanks its genetic algorithm.https://github.com/accsc/GAsol. BSD 3-clauses...
Green solvents made from glycerol change the classical regioselectivity of Biolacta No 5 β-galactosidase, β(1→4) to β(1→6) linkages when a 2 M concentration was used. In order explain these results, non-proteic compounds present in preparation were separated by precipitation with ammonium sulfate and remaining protein extract used set reactions appropriate organic find that towards isomer is retained. According proteomic analysis, 98% homology between Streptococcus pneumoniae β-galactosidase...
Predicting the cellular response of compounds is a challenge central to discovery new drugs. Compound biological signatures have risen as way representing perturbation produced by compound in cell. However, their ability encode specific phenotypic information and generating tangible predictions remains unknown, mainly because inherent noise such data sets. In this work, we statistically aggregate signals from several find that produce desired phenotype We exploit method two applications...
Background: Diarrhoea remains one of the leading causes childhood mortality globally. Recent epidemiological studies conducted in low-middle income countries (LMICs) identified Shigella spp. as first and second most predominant agent dysentery moderate diarrhoea, respectively. Antimicrobial therapy is often necessary for infections; however, we are reaching a crisis point with efficacious antimicrobials. The rapid emergence resistance against existing antimicrobials poses serious global...
Highlights•RPE model to investigate the consequences of pathological HtrA1 overexpression•Increase transcriptional levels lead tubulin intracellular degradation.•Overexpression leads 2-fold reduction in stiffness RPE cells.•HtrA1 increase translates into impaired apical processes and phagocytic activity.Age-related macular degeneration (AMD) is an eye disease which may result blurred or no vision it associated with a malfunctioning retinal pigment epithelium (RPE) back retina tissue. The...
Background and Purpose Some existing computational methods are used to infer protein targets of small molecules can therefore be find new for drugs, with the goals re‐directing molecule towards a different therapeutic purpose or explaining off‐target effects due multiple targeting. Inherent limitations, however, arise from fact that chemical analogy is calculated on basis common frameworks scaffolds also because target information neglected. The method we present addresses these issues by...
An efficient deacylation of peracetylated pyranosides has been developed in different biosolvents, catalyzed by <italic>Pseudomonas stutzeri</italic> lipase, which displayed regiospecific activity towards the anomeric position.
A green synthesis for β-(1→3) galactosyldisaccharides that combines the use of a biodegradable biocatalyst, aqueous solutions, and solvent recycling (renewable derived from biomass) has been developed. The biomass-derived solvents allows good catalytic activity in Gal-β-D-(1→3)GlcNAc Gal-β-D-(1→)3GalNAc (99% 95% yields respectively) with β-Gal-3-NTag β-galactosidase, preventing hydrolytic full regioselectivity. This represents considerable improvement over an buffer or conventional organic...
An ultrafast docking and virtual screening program, CRDOCK, is presented that contains (1) a search engine can use variety of sampling methods an initial energy evaluation function, (2) several minimization algorithms for fine tuning the binding poses, (3) different scoring functions. This modularity ensures easy configuration custom-made protocols be optimized depending on problem in hand. CRDOCK employs precomputed library ligand conformations are initially generated from one-dimensional...