13 research outputs found
Correlation between flexibility of chain-like polyelectrolyte and thermodynamic properties of its solution
Structural and thermodynamic properties of the model solution containing
charged oligomers and the equivalent number of counterions were studied by
means of the canonical Monte Carlo simulation technique. The oligomers are
represented as (flexible) freely jointed chains or as a linear (rigid) array of
charged hard spheres. In accordance with the primitive model of electrolyte
solutions, the counterions are modeled as charged hard spheres and the solvent
as dielectric continuum. Significant differences in the pair distribution
functions, obtained for the rigid (rod-like) and flexible model are found but
the differences in thermodynamic properties, such as, enthalpy of dilution and
excess chemical potential, are less significant. The results are discussed in
light of the experimental data an aqueous polyelectrolyte solutions. The
simulations suggest that deviations from the fully extended (rod-like)
conformation yield slightly stronger binding of counterions. On the other hand,
the flexibility of polyions, even when coupled with the ion-size effects,
cannot be blamed for qualitative differences between the theoretical results
and experimental data for enthalpy of dilution.Comment: 14 pages, 10 figure
Cross-recognition of a pit viper (Crotalinae) polyspecific antivenom explored through high-density peptide microarray epitope mapping
Snakebite antivenom is a 120 years old invention based on polyclonal mixtures of antibodies
purified from the blood of hyper-immunized animals. Knowledge on antibody recognition
sites (epitopes) on snake venom proteins is limited, but may be used to provide molecular
level explanations for antivenom cross-reactivity. In turn, this may help guide antivenom
development by elucidating immunological biases in existing antivenoms. In this study, we
have identified and characterized linear elements of B-cell epitopes from 870 pit viper venom
protein sequences by employing a high-throughput methodology based on custom designed
high-density peptide microarrays. By combining data on antibody-peptide interactions with
multiple sequence alignments of homologous toxin sequences and protein modelling, we
have determined linear elements of antibody binding sites for snake venom metalloproteases
(SVMPs), phospholipases A2s (PLA2s), and snake venom serine proteases (SVSPs). The
studied antivenom antibodies were found to recognize linear elements in each of the three
enzymatic toxin families. In contrast to a similar study of elapid (non-enzymatic) neurotoxins,
these enzymatic toxins were generally not recognized at the catalytic active site responsible
for toxicity, but instead at other sites, of which some are known for allosteric inhibition or for
interaction with the tissue target. Antibody recognition was found to be preserved for several
minor variations in the protein sequences, although the antibody-toxin interactions could
often be eliminated completely by substitution of a single residue. This finding is likely to have
large implications for the cross-reactivity of the antivenom and indicate that multiple different
antibodies are likely to be needed for targeting an entire group of toxins in these recognized
sites.Novo Nordisk Foundation/[NNF13OC0005613]/NNF/DinamarcaNovo Nordisk Foundation/[NNF16OC0019248]/NNF/DinamarcaUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP