Research

Bioinformatics of protein function and interactions

Understanding how proteins recognize each other complements information on protein binding in a way that brings us necessary insights into how both high affinity and high specificity are achieved.

Our recent papers on protein interactions and cellular mechanisms:

• Veljkovic et al. Influenza vaccine as prevention for cardiovascular diseases: Possible molecular mechanism. Vaccine. 2014. pii: S0264-410X(14)00933-5.
• Mancini et al. Cytoplasmatic compartmentalization by Bcr-Abl promotes TET2 loss-of-function in chronic myeloid leukemia. J Cell Biochem. 2012. 113(8):2765-74.
• Veljkovic et al. Physical activity and natural anti-VIP antibodies: potential role in breast and prostate cancer therapy. PLoS One. 2011. 6(11):e28304.
• Veljkovic et al. Characterization of conserved properties of hemagglutinin of H5N1 and human influenza viruses: possible consequences for therapy and infection control. BMC Struct Biol. 2009. 9:21.

Understanding consequences of genetic variation

Many bioinformatics tools are being developed to screen for potentially deleterious SNPs, with the aim of replacing expensive laboratory analyses. We are performing systematic evaluation of the effects of gene mutations and single amino acid substitution on the function of human and viral proteins. Recently, the ISM-based phylogenetic approach has been applied to the assessment of functional evolution of protein sequences.

Some of our recent papers on gene variation analyses include:

• Perovic et al. Novel phylogenetic algorithm to monitor human tropism in Egyptian H5N1-HPAIV reveals evolution toward efficient human-to-human transmission. PLoS One. 2013. 26;8(4):e61572.
• Gemovic et al. Feature-based classification of amino acid substitutions outside conserved functional protein domains. Scientific World Journal. 2013. 17;2013:948617.
• Perovic. Novel algorithm for phylogenetic analysis of proteins: application to analysis of the evolution of H5N1 influenza viruses. J Math Chem. 2013. vol. 51 br. 8, str. 2238-2255.

Drug and therapeutics research

Proteins are responsible for nearly every task of cellular life and most diseases are caused by abnormalities in the expression or function of proteins. It is therefore not surprising that proteins are the most attractive drug targets in the pharmaceutical industry. With the continuing decrease in sequencing costs there is an urgent need for the development of computational methods that are expected to accelerate the therapeutics discovery pipeline. We are applying computer-aided molecular analyses that simplify the screening of chemical libraries and de novo peptide design with assigned biological activity.

Some of our papers on drug-like molecules screening and bioactive peptide design:

• Veljkovic et al. The role of long-range intermolecular interactions in discovery of new drugs. Expert Opin Drug Discov. 2011. 6(12):1263-70.
• Nikolic et al. Imidazoline-1 receptor ligands as apoptotic agents: pharmacophore modeling and virtual docking study. Comb Chem High Throughput Screen. 2013. 16(4):298-319.
• Vergara-Alert et al. Conserved synthetic peptides from the hemagglutinin of influenza viruses induce broad humoral and T-cell responses in a pig model. PLoS One. 2012. 7(7):e40524.
• Veljkovic et al. Can natural antibodies to VIP or VIP-like HIV-1 glycoprotein facilitate prevention and supportive treatment of breast cancer? Med Hypotheses. 2011. 77(3):404-8.