In silico studies of the interaction between BRN2 protein and MORE DNA.

The incidence of skin cancer has increased in recent decades, and melanoma is the most aggressive form with the lowest chance of successful treatment. Currently, drug design projects are in progress, but available treatments against metastatic melanoma have not significantly increased survival, and few patients are cured. Thus, new therapeutic agents should be developed as more effective therapeutic options for melanoma. High levels of the BRN2 transcription factor have been related to melanoma development. However, neither the three-dimensional (3D) structure of BRN2 protein nor its POU domain has been determined experimentally. Construction of the BRN2 3D structure, and the study of its interaction with its DNA target, are important strategies for increasing the structural and functional knowledge of this protein. Thus, the aim of this work was to study the interaction between BRN2 and MORE DNA through in silico methods. The full-length BRN2 3D structure was built using the PHYRE2 and Swiss-Model programs, and molecular dynamics of this protein in complex with MORE DNA was simulated for 20 ns by the NAMD program. The BRN2 model obtained includes helix and loop regions, and the BRN2 POU domain shares structural similarity with other members of the transcription factor family. No significant conformational change of this protein occurred during dynamics simulation. These analyses revealed BRN2 residues important for the specific interaction with nucleotide bases and with more than one DNA nucleotide. This study may contribute to the design of inhibitors against BRN2 or MORE DNA as molecular targets of melanoma skin cancer. Graphical Abstract Model of complete Brn2 protein in complex with MORE DNA after building through comparative modeling and refinement by molecular dynamics simulation.

Cytotoxic Activities of Eosinophil Cationic Protein and Eosinophil-derived Neurotoxin: In Silico Analysis.

BACKGROUND: Eosinophil cationic protein (ECP) and eosinophil derived-neurotoxin (EDN) are homologous ribonuclease (RNAse) A family proteins. The objective of the present study was to in silico characterize ECP and EDN with respect to their cytotoxic activities. MATERIALS AND METHODS: Structural, physicochemical, and conserved domain characterizations were carried-out using open-source software, such as InterProScan, NetOGlyc, NetPhos and Discovery Studio 3.1. RESULTS: The proteins did not have atypical conserved domains. EDN had a greater number of glutamine amino acid residues, whereas ECP had a predominance of arginine. ECP had four possible N-glycosylation, three O-glycosylation and four phosphorylation sites. EDN had five putative N-glycosylation, three phosphorylation and no O-glycosylation sites. CONCLUSION: The greater cationicity of ECP may be related to its higher cytotoxicity and to the fact that the varying post-translational modification profiles can generate functional differences from structural alteration. In vivo and in vitro studies need to be performed in order to confirm these predictions.

Identification of a vaccine against schistosomiasis using bioinformatics and molecular modeling tools.

Schistosomiasis is a serious public health problem in Brazil and worldwide. Although the drugs used to treatment schistosomiasis are effective, the disease continues to expand in all endemic countries due to constant reinfection, poor sanitation, and the lack of effective programs for disease control. However, advances generated through genome projects have provided important information that has improved the understanding of the biology of this parasite. These advances, associated with the advent of bioinformatic analysis, are becoming an important tool in reverse vaccinology. Through database access to the DNA and protein sequences of Schistosoma mansoni and the use of bioinformatics programs, fourteen epitopes were identified. Five epitopes were obtained from proteins whose immunogenic potential had already been assessed in other studies (KP), and nine whose immunogenic potential is unknown (UP). To improve stimulation of the host immune system, the selected epitopes were modeled with a sugar moiety. After this addition, all of the epitopes showed structures similar to those observed in the native proteins, but only eleven of the peptides presented thermodynamically stable structures. Prediction analysis and molecular modeling showed that the glycopeptides presented here are important targets in the search for a vaccine against schistosomiasis. Additionally, they suggest that these molecules may be used in immunological assays to evaluate the level of protection, the effect on pathology reduction and the profile of cytokines and antibodies induced by them.