Studies on the interaction sites of peptide toxins and ion channels typically involve site-directed mutations in toxins. However, natural mutant toxins exist among them, offering insights into how the evolutionary process has conserved crucial sequences for activities and molecular target selection. In this study, we present a comparative investigation using electrophysiological approaches and computational analysis between two alpha toxins from evolutionarily close scorpion species of the genus Tityus, namely, Tst3 and Ts3 from T. stigmurus and T. serrulatus, respectively. These toxins exhibit three natural substitutions near the C-terminal region, which is directly involved in the interaction between alpha toxins and Nav channels. Additionally, we characterized the activity of the Tst3 toxin on Nav1.1-Nav1.7 channels. The three natural changes between the toxins did not alter sensitivity to Nav1.4, maintaining similar intensities regarding their ability to alter opening probabilities, delay fast inactivation, and induce persistent currents. Computational analysis demonstrated a preference for the down conformation of VSD4 and a shift in the conformational equilibrium towards this state. This illustrates that the sequence of these toxins retained the necessary information, even with alterations in the interaction site region. Through electrophysiological and computational analyses, screening of the Tst3 toxin on sodium isoform revealed its classification as a classic α-NaTx with a broad spectrum of activity. It effectively delays fast inactivation across all tested isoforms. Structural analysis of molecular energetics at the interface of the VSD4-Tst3 complex further confirmed this effect.

This study examines the statistical conditions of coevolutionary signals that allow algorithmic predictions of protein partners based on amino acid sequences rather than 3D structures. It introduces a Markov stochastic model that predicts the number of correct protein partners based on coevolutionary information. The model defines state probabilities using a Poisson mixture of normal distributions, with key parameters including the total number of protein sequences M, the coevolutionary information gap α, and variance σ₀². The model suggests that algorithmic approaches that maximize coevolutionary information cannot effectively resolve partners in protein families with a large number of sequences M ≥ 100. The model shows that true-positive (TP) rates can be enhanced by disregarding mismatches among similar sequences. This approach allows a distinction, in terms of {α, σ₀²}, between optimized solutions with trivial errors and other degenerate solutions. Our findings enable the a priori classification of protein families where partners can be reliably predicted by ignoring trivial errors between similar sequences, advancing the understanding of coevolutionary models for large protein data sets.

Os conteúdos de Astronomia são ministrados no Ensino Fundamental Anos Finais na disciplina de Ciências, por profissionais formados em Licenciaturas Científicas, como Ciências Biológicas. Nesse contexto, a formação inicial desses docentes é questionada, mas investigações sobre o currículo desses cursos para o ensino de Astronomia são escassas. Com isso, o objetivo desse trabalho foi analisar os currículos dos cursos de Licenciatura em Ciências Biológicas das Universidades Federais do Brasil em relação aos conteúdos de Astronomia. Para isso, foi realizado um estudo exploratório que utiliza como método a pesquisa documental, através da busca de palavras-chave relacionadas a Astronomia, nos Projetos Pedagógicos dos Cursos. As disciplinas e conteúdos de Astronomia encontrados foram classificados conforme a Análise de Conteúdo de Bardin. Foram analisadas 55 instituições do total de 61 Universidades Federais Brasileiras que possuem curso de Licenciatura em Ciências Biológicas. Dessas, apenas 18 possuem conteúdos de Astronomia no currículo. Ao todo, foram encontradas 23 disciplinas, sendo que apenas quatro possuem a ementa composta exclusivamente por conteúdos de Astronomia. Por fim, o presente estudo corrobora a hipótese de que cursos de Biologia negligenciam os assuntos astronômicos e colabora com as discussões acerca da formação inicial de professores de Ciências para o ensino de Astronomia.