7^th International Conference on Bioinformatics October 24-25, 2016 Rome, Italy

Alena Dmitrievna Volyntceva is a Post-graduate student of Chair of Bioengineering at the Faculty of Biology, Lomonosov Moscow State University. She is the junior Reseacher and has been investigating receptor-ligand interactions for six years in the Laboratory of Molecular Dynamics and Molecular Modeling. Her current interests includes “Study of potassium channels interactions with scorpion toxins”.

The calcium-activated potassium channels (KCa channels) are widely expressed in the organism. Several studies demonstrated the potential role of KCa3.1 channel blockage as a therapeutic strategy. Knowledge of the molecular aspects of blockers binding process is an important step in designing highly efficient and selective ligands. Aim of this study was an interface analysis in complexes of hybrid channel KcsA-KCa3.1 with peptide blockers agitoxin, charybdotoxin and maurotoxin. KcsA-KCa3.1 chimera represents KcsA channel with P-loop taken from the human KCa3.1. 3D structure was generated by homology modeling using complex of mutated KcsA channel with charybdotoxin (pdb-code 2A9H) as a template. Molecular dynamic simulation was performed using Gromacs software. Optimal conformations of toxins in channel binding site were chosen from the trajectories. Hydrophobic and stacking interactions, hydrogen and ionic bonds of the toxins and hybrid channel were evaluated using program Platinum and APBS software package. Contacts energy characteristics evaluation showed that maurotoxin was the most effective blocker of KCa3.1 channel among these toxins. This result is in good agreement with the experimental data. Knowledge of channel-toxins interfaces allowed us to propose amino acid mutations in toxins to increase binding affinity and selectivity. Results of the conducted investigation are of great interest for drug development.

João Lídio da Silva Gonçalves Vianez Junior has completed his Graduation in Biological Sciences at the UFRJ, MSc in Plant Biotechnology at the UFRJ and PhD in Biological Sciences (Biophysics) at the same institution. Currently, he is a General Coordinator of the Center for Technological Innovation of Evandro Chagas Institute (IEC) and Coordinator of the Bioinformatics Core. He has experience in “Assembly, annotation of genomes and transcriptomics data from NGS platforms, modeling, molecular dynamics and anchoring”.

Brazil is facing an unprecedented growth in the number of microcephaly cases in babies. This phenomenon coincided with the recent Zika virus (ZIKV) outbreak in this country. Although the Brazilian Ministry of Health was quick to recognize that ZIKV was probably the cause of microcephaly in newborns, the underlying mechanisms leading to the development of this pathology have not been established. To tackle this problem at the molecular level, we employed whole transcriptome sequencing of human neurospheres derived from neural stem cells exposed to ZIKV isolated in Brazil (Asian genotype). Differential gene expression analysis of control (MOCK) and ZIKV infected neurospheres generated a list of 26 down-regulated and 64 up-regulated genes. Among the up-regulated detected genes, the cyclin-dependent kinase inhibitor 1A (CDKN1A) and the glial fibrillary acidic protein gene (GFAP) were found. CDKN1A prevents the activation of the cyclin E/CDK2 complex, acting as a regulator of cell cycle progression during G1 and GFAP is a known marker of astrocytes. We also observed a decrease in the expression of the neurogenic differentiation 1 gene (NEUROD1) which is directly involved in the neurogenic program. Those findings suggest that ZIKV infection induces cell cycle arrest and inhibits the neuronal differentiation, resulting not only in the reduction of the size but in a deeper disruption of the normal development of the human brain.