6^th International Conference on Bioinformatics & Systems Biology August 22-23, 2016 Philadelphia, Pennsylvania, USA

Ruchika Bhat is currently pursuing her second year of PhD from the Department of Chemistry at IIT Delhi. She has previously worked as Project Assistant in IIIM Jammu (CSIR Lab) for a tenure of 10 months before joining PhD. Her areas of experties lies in Computional Biology, Computer Aided Drug Designing, Bioinformatics, etc. She has done BE in Biotechnology from University of Mumbai in the year 2010. She has completed her MTech in Bioinformatics from Jamia Hamdard University, New Delhi.

Dhanvantari: An automated pipeline starting from genome sequence leading to small molecules as potential drugs. It is a unique assembly of several independent programs developed by our team at Supercomputing Facility for Bioinformatics and Computational Biology, IIT Delhi. First module i.e ChemGenome, reveals the amino acid sequences, a given genome codes for. These predicted protein sequences are then fed to Bhageerath+which generates tertiary structures, ranked based on ProtSAV+Active Site finder (ASF) utilizes structure information to specify their respective active sites. A rapid screening (RASPD) against a molecular database, selects the best hits (small molecules) against all predicted active sites. Docking (ParDOCK) further refines hits and generates their best binding poses. Further, a short molecular dynamics simulation run on the selected pose brings valuable insights about the in vivo drug receptor interactions. Molecules found with stable binding affinity throughout are finally presented as potential drugs which could then be separately investigated in vitro. As of 2016, obtaining a drug molecule from just genomic information is a grand challenge. Dhanvantari is thus a vital contribution to the drug discovery community. This software suite aims at speeding up the drug discovery process to save time and resources without compromising on efficacy, apart from automating to make it user friendly. Case studies on HAV and HBV genomes lead to hit molecules through this protocol and their in vitro testing is underway at KSBS, IIT Delhi. This suite will be updated and revised regularly to keep up the standards of high level performance.

Maninder Kaur is persuing her PhD from Punjabi University Patiala in the Department of Pharmaceutical Sciences and Drug Research. She has been awarded Gold Medal in MPharmacy in Pharmaceutical Chemistry from the same university. She has published more than 25 papers in reputed international journals.

Among various kinase family members, Syk (spleen tyrosine kinase) and JAK3 (Janus kinase 3) have emerged as key players in immune cell signaling. Both the kinases have been implicated in autoimmune disorders such as rheumatoid arthritis, psoriasis etc. In last few years several Syk and JAK3 inhibitors have been reported in literature to reach later phases in the clinical trials. Fostamatinib (R788), an orally available Syk inhibitor is now in Phase III for RA. The major milestone for the use of kinase inhibitors for autoimmune disorders is the recent FDA approval of tofacitinib a JAK3 inhibitor. PRT062070, a novel dual inhibitor of Syk and JAK3 entered clinical trials announced by Portola Pharmaceuticals. In the light of above, Syk and JAK3 dual inhibitors can offer scientific and rational treatment for complex autoimmune disorders. In the present study, LBPM were developed for Syk and JAK3 using diverse Syk and JAK3 inhibitors. The best models for Syk (ADPR.14) and JAK3 (AADH.54) were selected on the basis of highest value of Q2test. The selected models were then modified manually on the basis of e-pharmacophore models generated for highest active and clinical trial inhibitors for both Syk and JAK3. The modified pharmacophores for Syk (APDRR.14) and JAK3 (AAHDR.54) were validated and employed for screening of Asinex database followed by docking based screening. The hits with pharmacophoric features and essential docking interactions for both enzymes were further employed for pharmacokinetic properties and MM-GBSA energy calculation. The systematic ligand and structure based modelling strategies lead to nine hits as dual inhibitors of Syk and JAK3. Among them top two hits were validated by molecular dynamics. Thus these dual inhibitors can be further explored as therapeutics for autoimmune disorders.

James Villanueva is the recipient of the DuPont – National Academy of Science and Technology Young Scientist Award in 2003 and has been teaching Medical Biochemistry, Genetics and Nutrition at IAU since 2005. He received the IAU Faculty of the Year Award in 2006 and was appointed as the Dean of Student Affairs in 2007 and elected Chairman of the Admissions Committee in 2008. His research interests include protein folding/misfolding, protein spectroscopy, development of immunoliposomes and biodesulfurization. He has completed Post-Doctoral research work at Notre Dame University in Indiana; The Institute for Protein Research, Osaka University, Japan and Bari University, Italy. Over the years, he has consistently made outstanding contribution to student success in NBME Shelf exams and is closely associated with the university student community as the Faculty Advisor to the Student Government Association (SGA). He was promoted to full Professor of Biochemistry, Genetics and Nutrition in September of 2011 and then as the Dean of Basic Sciences in 2014, he continues to inspire and be inspired by academia.

Familial amyotropic lateral sclerosis (ALS) has been linked with mutant misfolded superoxide dismutase (SOD) aggregates in motor neurons. Although the aggregation pathway has not yet been fully elucidated, the use of naturally occurring polyphenols to inhibit this deleterious process shows pharmacologic potential for intervention. Curcumin, the polyphenolic active component of turmeric, has been demonstrated to have inhibitory properties against the aggregation of a broad spectrum of misfolded proteins. Using Autodock Vina, Autodock tools and Discovery Studio Visualizer, both the keto and enol forms of curcumin as well as chlorogenic acid, a curcuminoid, were docked with A4V and I113T, two prevalent mutants of SOD and the protein in its wild type configuration, comparing metal bound versus apo versions of the protein. Putative binding sites as well as ligand binding affinities and protein bound configurations were determined and analyzed. The results indicate that the ligands form stable complexes with these proteins, with chlorogenic acid exhibiting higher levels of binding affinities for the two mutants and wild type SOD.

Amakiri Augustine is currently a Master’s student at the University of Liverpool. He completed his undergraduate studies at Federal University of Technology, Owerri where he obtained a Bachelor’s degree in Microbiology.

The research is aimed at studying medin, a protein implicated in cardiovascular disease through deposition as insoluble fibrillar aggregates in the medial layer of the aorta. Medin is a 50 amino acid protein located at the Cterminal of the C2 domain of lactadherin. The process by which medin is cleaved out of the C2 domain in cardiovascular disease is yet unknown hence the need for further studies. There are currently two pdb structures available for lactadherin C2 domains: bovine (2PQS) and mouse (2L9L). This research has identified significant variation within the medin sequence when comparing human medin to bovine and mouse medin. Results from aggregation prediction studies showed that human medin contains three regions located at positions 914, 3337 and 4450 with very high propensity to form aggregates while the bovine and mouse model contained two regions each located at positions 3337 and 4440. This result validates the theory that sequence variations between the medin sequence in these species have a significant impact on the behaviour of the protein. Knowledge gained from studying the sequence variation and aggregation properties of medin in these species will be applied to enhance understanding of how medin may be cleaved from the C2 domain and form insoluble fibrillar aggregates in cardiovascular disease.