Biology subjects

Coll, J.

Publications and source records attributed to Coll, J..

6 recordsLinked to original sources

bioRxiv2025

Plasmodium killing and antimicrobial lineal or cyclic-peptides computationally targeted the circumsporozoite CSP protein

The RT39 amphipathic lineal-peptide (ALP), described as the faster membranolytic-killer of circumsporozoite Plasmodium falciparum (Aguirre-Botero et al, 2024), computationally predicted the highest affinities to the external circumsporozoite protein (CSP), compared to other described ALPs. Additional computational co-cyclizations of CSP/ALPs generated CSP/cycRT39 cyclic-conformers predicting the highest picoMolar affinities to target CSP-TSR domains with de novo alternative amino acid sequences, proteolytic resistance, and chemical stability. A preliminary co-screening of Uniprot antimicrobial peptides (AMPs), discovered some CSP/cycAMP-conformers predicting similar high affinities. These novel cycALP and/or cycAMP amino acid sequences may deserve experimental validation tests. Could some of them help to advance on circumsporozoite interference in mosquitos and/or humans?. O_FIG O_LINKSMALLFIG WIDTH=147 HEIGHT=200 SRC="FIGDIR/small/679691v1_ufig1.gif" ALT="Figure 1"> View larger version (49K): org.highwire.dtl.DTLVardef@894c28org.highwire.dtl.DTLVardef@1e70fd0org.highwire.dtl.DTLVardef@bf448aorg.highwire.dtl.DTLVardef@12ce348_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2025

Targeting Listeria virulence-regulon glutathion-cavity by evolutecas

Computational explorations are described by screening and generating peptide and acetic-polymer evolutecas targeting one of the virulence regulons of Listeria monocitogenes (Lm). Lm are among the most important multiple-resistant food-borne infective bacteria whose antibiotic resistances raise worldwide concerns. The Lm glutathion cavity called positive regulatory factor A (prfA) virulence regulon, was computationally targeted here because of the glutathion-dependent prfA activation of many Lm virulent genes. Computationally docking screening of both tri-,tetra-, and penta-mer peptides or innovative acetic-polymers (mimicking amino acids) and evolutecas generating thousands of ligand candidates, were employed to optimize their fitting to glutathion-prfA cavities. Combining library-screenings and evoluteca generations, novel top-peptides and top-acetic-polymers were generated predicting both low-toxicities (to reduce any known undesirable side-effects) and low nanoMolar consensus affinities (to maximize their specificities). Co-evolved top-acetic-polymer smiles were also co-folded to prfA amino acid sequence (ligand-induced-fit) by deep-learning Boltz2. Comparative ADV and Boltz2 results confirmed similar targeted cavity and most top-ligand affinities, despite their sharply different algorithms. Whether some of the top affinities / conformations correspond to the most active prfA inhibitors will only depend on experimental validation. Therefore, some additional chemical synthesis and in vitro experimental validation, are strictly required to continue with the Lm prfA virulence explorations. O_FIG O_LINKSMALLFIG WIDTH=127 HEIGHT=200 SRC="FIGDIR/small/658548v2_ufig1.gif" ALT="Figure 1"> View larger version (56K): org.highwire.dtl.DTLVardef@185db32org.highwire.dtl.DTLVardef@f9d139org.highwire.dtl.DTLVardef@117136eorg.highwire.dtl.DTLVardef@1fccfa2_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

bioRxiv2021

Prediction of nanographene binding-scores to trout cellular receptors and cytochromes

To address the increasing concerns surrounding possible impacts of graphene-related materials on the aquatic environment, this study focused on computational predictions of binding between models of graphenes in the nm size range (nanographenes, nGs) and the aryl-hydrocarbon receptor (tAHR) and P450 cytochromes (tCYPs) of rainbow trout (Oncorhynchus mykiss). The tAHR plays a key role in the induction of detoxifying and early immune responses and tCYPs are essential for detoxifying planar hydrophobic chemicals such as nGs. After 3D modelling of those trout proteins, docking algorithms predicted the size-dependance profiles of nGs binding-scores to tAHR and tCYPs in the low nM range (high binding-affinities). Virtual oxidations of nGs to nGOs (carboxy-, epoxy-and/or hydroxy-oxidations) further lowered the corresponding binding-scores in level/type-oxidation manners. Among all the tCYPs, the tCYP3AR (the equivalent to human CYP3A4) was identified as a potential key interaction enzyme for nGs because of its lower binding-scores. These results implicate a possible processing pathway to be further probed through in vitro and in vivo experimentation. Together the information generated can be pivotal for the design of safer graphene-related materials for a variety of applications and help to understand their detoxification in aquatic vertebrates.

pharmacology and toxicology↗

bioRxiv2021

Computational ligands to VKORC1s and CYPs. Could they predict new anticoagulant rodenticides?

Anticoagulant-resistance in rodents and anticoagulant off-target effects are some of the world-wide problems of increasing concern. To search for new anticoagulant rodenticide candidates we have computationally explored some of the rat genes previously implicated in resistance to actual anticoagulants. In particular, we searched among hundreds of anticoagulant-similar chemotypes those binding rat wild-type VKORC1 (the best-known anticoagulant target, a Vitamin K-recycling enzyme), VKORC1L1 (a VKORC1-related enzyme), Cytochrome P450 CYP enzymes (some of the most important enzymes implicated in detoxification) and anticoagulant-resistant VKORC1-mutants (to minimize propensity to resistance). Results predicted new VKORC1 leads with binding-scores in the low nM range (high binding-affinities) predicting hydroxycoumarin- and naphtoquinone-like chemotypes. We then selected top-leads with additional high binding-scores to more than three anticoagulant-related CYPs, suggesting minimal detoxification rates and therefore maximal anticoagulation expectatives. A downsized list of top top-leads maintaining VKORC1 low-binding scores to anticoagulant resistant mutants, was finally proposed for experimental validation. The combination of different rat targets for computational studies, could be used to search for unrelated chemotypes, for reduction of off-target environmental anticoagulant impacts, and/or as new tools to explore anticoagulant molecular mechanisms.

pharmacology and toxicology↗

bioRxiv2018

Host genetic associations with the gut microbiota in HIV-1-infected subjects: a pilot exploratory study

The impact of host genetics on gut microbial dynamics is debated. No study to date has investigated the possible role of host genetics in shaping the gut microbiota in HIV-1 infected subjects. With the aim of generating preliminary data to inform future host genetic studies, we performed an exploratory host exome analysis of 147 subjects either infected or at risk of becoming infected with HIV-1 from the MetaHIV cohort in Barcelona. Using a DNA microarray chip, we sought to identify host genetic variants associated to three specific microbial features with a potentially inheritable component, and which were previously found to be associated with gut dysbiosis in HIV infection, i.e.: gut enterotype, presence of methanogenic archaea and microbial gene richness. After correction for multiple comparisons, we did not observe any statistically significant association between the hosts genetic landscape and the explored gut microbiome traits. These findings will help design future, adequately-powered studies to assess the influence of host genetics in the microbiome of HIV-1-infected subjects.

genomics↗

bioRxiv2018

25-HYDROXYL-CHOLESTEROL BINDS AND ENHANCE ANTI-VIRAL EFFECTS OF ZEBRAFISH MONOMERIC C-REACTIVE PROTEINS

C-reactive proteins (CRP) are among the faster acute-phase inflammation-responses coded by one gene in humans (hcrp) and seven genes (crp1-7) in zebrafish (Danio rerio). In this study, preferential 25-hydroxycholesterol (25HOCh) binding to zebrafish CRP1-7 compared to other lipids were predicted by in silico docking and confirmed by solid-phase binding-assays. In addition, 25HOCh enhanced methyl-betacyclodextrin-sensitive (Cholesterol-dependent) CRP1-7 anti-viral effects in a fine-tunned isoform-dependent manner. In silico and structural studies suggested that the crosstalk between the anti-viral enhancements of both 25HOCh and CRP1-7 were dependent on protein monomers rather than oligomers but differred among isoforms. The presence of oxidized cholesterols in human atherosclerotic plaques amplifies the importance that similar interactions may have for vascular and/or neurodegenerative diseases during viral infections. In this context, the zebrafish model offers a genetic tool to further investigate how the expression and functions of different CRP isoforms and/or transcript variants may be controlled.

immunology↗