RESUMO

Organic dendrimers with π conjugated systems are capable of capturing solar energy as a renewable source for human use. Nonetheless, further study regarding the relationship between the structure and the energy transfer mechanism in these types of molecules is still necessary. In this work, nonadiabatic excited state molecular dynamics (NEXMD) were carried out to study the intra- and inter-branch exciton migration in two tetra-branched dendrimers, C(dSSB)4 and Ad(BuSSB)4, which differ in their respective carbon and adamantane core. Both systems undergo a ladder decay mechanism between excited states, with back-and-forth transitions between S1 and S2. Despite presenting very similar absorption-emission spectra, differences in the photoinduced energy relaxation are observed. The size of the core impacts the inter-branch energy exchange and transient exciton localization/delocalization, which ultimately condition the relative energy relaxation rates, being faster in Ad(BuSSB)4 with respect to C(dSSB)4. Nevertheless, the photoinduced processes lead to a progressive final exciton-self-trapping in one of the branches of both dendrimers, which is a desirable feature in organic photovoltaic applications. Our results can inspire the design of more efficient dendrimers with the desired magnitude of inter-branch exciton exchange and localization/delocalization according to changes in their core.

RESUMO

A structural analysis over various spike proteins from three highly pathogenic Betacoronavirus was done to understand their structural differences. The proteins were modeled using crystal structures from SARS-CoV, MERS-CoV, and other Betacoronavirus that infect bats and pangolins. The group was split in two sets; the first set corresponds to the non-mutated spike proteins, while the second set corresponds to mutated spike variants alpha, beta, gamma, delta, omicron and mu; five of them classified as variants of concern and the last one as variant of interest. A conformational space exploration was carried out for every protein by using molecular dynamic simulations. Root mean square fluctuations, principal component and cross-correlation analysis were carried out over the dynamics to analyze the flexibility and rigidity of every protein in comparison to the wild type Spike protein from the SARS-CoV-2. The obtained results indicate that the proteins, which are not spread among humans, have smooth movements compared to those of SARS-CoV-2 and its variants. In addition, a relationship between the speed of the virulence and the movement of the protein can explain the behavior of delta and omicron variants.

Assuntos

RESUMO

FimH is a type I fimbria of uropathogenic Escherichia coli (UPEC), recognized for its ability to adhere and infect epithelial urinary tissue. Due to its role in the virulence of UPEC, several therapeutic strategies have focused on the study of FimH, including vaccines, mannosides, and molecules that inhibit their assembly. This work has focused on the ability of a set of monosubstituted and disubstituted phenyl mannosides to inhibit FimH. To determine the 3D structure of FimH for our in silico studies, we obtained fifteen sequences by PCR amplification of the fimH gene from 102 UPEC isolates. The fimH sequences in BLAST had a high homology (97-100%) to our UPEC fimH sequences. A search for the three-dimensional crystallographic structure of FimH proteins in the PDB server showed that proteins 4X5P and 4XO9 were found in 10 of the 15 isolates, presenting a 67% influx among our UPEC isolates. We focused on these two proteins to study the stability, free energy, and the interactions with different mannoside ligands. We found that the interactions with the residues of aspartic acid (ASP 54) and glutamine (GLN 133) were significant to the binding stability. The ligands assessed demonstrated high binding affinity and stability with the lectin domain of FimH proteins during the molecular dynamic simulations, based on MM-PBSA analysis. Therefore, our results suggest the potential utility of phenyl mannoside derivatives as FimH inhibitors to mitigate urinary tract infections produced by UPEC; thus, decreasing colonization, disease burden, and the costs of medical care.

RESUMO

Inositol polyphosphate 5-phosphatase (OCRL-1) participates in the regulation of multiple cellular processes, through the conversion of phosphatidylinositol 4,5-phosphate to phosphatidylinositol 4-phosphate. Mutations in this protein are related to Lowe syndrome (LS) and Dent-2 disease. In this study, the impact of Lowe syndrome mutations on the interactions of OCRL-1 with other proteins was evaluated through bioinformatic and computational approaches. In the functional analysis of the interaction network of the proteins, we found that the terms of gene ontology (GO) of greater significance were related to the intracellular transport of proteins, the signal transduction mediated by small G proteins and vesicles associated with the Golgi apparatus. From the proteins present in the GO terms of greater significance Rab8a was selected because its interaction facilitates the intracellular distribution of OCRL-1. The mutation p.Asn591Lys, present in the interaction domain of OCRL-1 and Rab8a, was studied using molecular dynamics. The molecular dynamics analysis showed that the presence of this mutation causes changes in the positional fluctuations of the amino acids and affects the flexibility of the protein making the interaction with Rab8a weaker. Rab proteins establish some specific interactions, which are important for the intracellular localization of OCRL-1; therefore, our findings suggest that the phenotype observed in patients with LS, in this case, is due to the destabilizing effect of p.Asn591Lys affecting the localization of OCRL-1 and indirectly its 5-phosphatase activity in the Golgi apparatus, endosomes, and cilia.

Assuntos