Biosciences Working Group Update Wilfred W. Li, Ph.D., UCSD, USA Habibah Wahab, Ph.D., USM, Malaysia Hosted by Monash University Melbourne, Australia, Apr 17-19, 2012

Transparent access of applications on Avian Flu Grid through middleware CNIC Duckling Portal Konkuk/Kukmin Glyco-M*Grid NBCR CADD

Phylogenetic analysis based upon representative NA sequences and structures Human Swine origin Avian origin *structure available Li et al, Nat Struc Mol Biol, 2010

2009 N1 Crystal does not contain 150 cavity Li et al, Nat Struc Mol Biol, 2010

Group 1 and 2 neuraminidases 2 phylogenetically distinct groups: Recently a crystal structure for N1 (a group 1 NA) was released. This structure revealed a flexible loop and a new pocket adjacent to the active site that can potentially exploited for drug discovery against this enzyme. Russell et al, Nature, 443: 45-49 (2006). Amaro et al, JACS, 2007

C-3 Derivatives of Zanamivir-like Compounds Lock 150 Cavity Open Oseltamivir N8 structure used Rudrawar et al, Nat Comm, 2011

2012 Transmissible H5N1 Mutations N158D T318I, N224K anitbody Q226L Newhouse et al, JACS 2009

New Class of HIV Drugs: Merck & Co. Relaxed Complex Scheme and Ensemble based Virtual Screening Contributed to HIV Integrase Inhibitor Development Discovery of unexpected binding site in HIV-1 Integrase using MD and AutoDock: Schames, … & McCammon, J. Med. Chem. (released on web, early 2004) “ Exploration of the structural basis for this unexpected result … suggests an approach to the development of integrase inhibitors with unique resistance profiles.” D. Hazuda et al., Proc. Natl. Acad. Sci. USA (Aug. 2004), refers to Schames, et al. (2004). MK-0518 February, 2006 – Phase III Clinical Trials February, 2007 – Name announced: Isentress (raltegravir) October, 2007 – FDA “fast track” approval New Class of HIV Drugs: Merck & Co. Source: A. McCammon

Relaxed complex scheme Infectious Diseases: HIV Influenza Virus Dengue Virus Neglected Diseases: African Sleeping Sickness Neurological Disorders: Alzheimer’s Disease Amaro, Baron, and McCammon, J. Comp. Aid. Mol. Des.. (2008) Amaro & Li, Curr. Top. Med. Chem. (2009) Amaro & Li, Methods in Mol Bio, (2012).

Opal WS: Transparent Access Layer for Applications Opal App MGLTools CADD Taverna Vistrails Kepler Opal Application Services Grid/Cloud Resources CSF4/Globus Condor Fork Condor pool TeraGrid/PRAGMA Grid PBS/SGE Clusters Applications are first class services - users don’t have to specify paths to executables, working directories, etc Examples of what the operations may look like 2. Security, state management, scheduling are all configured optionally 1. Jobs can even run on a Windows box - without a scheduler 3. Different services can exist in the same container - all accessible by separate URLs 4. Clients send command line arguments and input files to services (Base64 binary)

Virtualization for Bioscience Applications

Opal Plugins for Popular Workflow Software

Opal Web Service Client http://opal-duckling.escience.cn http://ws.nbcr.net/opal2/dashboard OPAL Services @ NBCR DUCKLING Portal @ CNIC Output URL User Management Job Result Opal Web Service Client Web Service Application UIs Submit Job (Service URL) Metadata Cache Opal Service List Job History Application Metadata

InSilicoCell System architecture Client Tool TEXT MINING SYSTEM Web Services (OPAL2) NCBI data downloader MetaMap Network Generator Sentence selector Information element recognizer Visualizer Data handler Relation extractor Information handler KISTI, Seok Jong Yu

BioKnowledge Viewer GUI

University of Indonesia Progress Update Member (alphabethicaly ordered) Abdul Mun'im (Phytochemistry) Alhadi Bustamam (GPU Computing) Arry Yanuar (Pharmaceutical Chemistry) Heru Suhartanto (High Performance and Numerical Computing)

University of Indonesia Working Group Database Prototype of Medicinal Plants Database and Three Dimensional Structure of the Chemical Compounds from Medicinal Plants in Indonesia, http://herbaldb.farmasi.ui.ac.id Medicinal Plants Database and Three Dimensional Structure of the Chemical Compounds from Medicinal Plants in Indonesia, Int J Comp Sci Issue, 2011, 8(5):180-183 Member : Prof. Heru Suhartanto, Ph.D (High Performance and Numerical Computing) Dr. Arry Yanuar (Pharmaceutical Chemistry) Alhadi Bustamam, Ph.D. (GPU Computing) Dr. Abdul Mun'im (Phytochemistry)

University of Indonesia Working Group Recent Publication (ordered based on author in the previous slide) Berna Elya, Katrin Basah, Abdul Mun'im, Wulan Yuliastuti, Anastasia Bangun, and Eva Kurnia Septiana, Screening of 𝛼-Glucosidase Inhibitory Activity from Some Plants of Apocynaceae, Clusiaceae, Euphorbiaceae, and Rubiaceae, Journal of Biomedicine and Biotechnology, Volume 2012 (2012), Article ID 281078, 6 pages, doi:10.1155/2012/281078 Bustamam A, Burrage K, Hamilton NA., Fast Parallel Markov Clustering in Bioinformatics using Massively Parallel Computing on GPU with CUDA and ELLPACK-R Sparse Format. IEEE/ACM Trans Comput Biol Bioinform. 2011 Mar 30. Hayun, Arry Yanuar, Muhammad Hanafi, and Sumi Hudiyono PWS, Virtual Screening of 2,3-Disubstituted-4(3H)-Quinazolinones Possessing Benzenesulfonamide Moiety for Selective COX-2 Inhibitor., Bioinformation. 2011; 7(5): 246–250 Heru Suhartanto, Arry Yanuar , M.H. Hilman, Ari Wibisono and Toni Dermawan, Performance Analysis Cluster Computing Environment on Molecular Dynamics Simulation of RAD GTPase and LOX-Curcumin Molecule with AMBER, Int J Comp Sci Issue, 2012, Vol. No. 2 (in-press).

University of Indonesia Working Group On progress Research Activities In Silico Screening of Antimalarial Activity from Indonesian Medicinal Plants Database. In Silico Screening of HIV-1 Enzymes inhibitor Activity from Indonesian Medicinal Plants Database in GPU Environment. Alpha-glucosidase inhibition activity from Indonesian Medicinal Plants Design and synthesis of new COX-2 inhibitor.

2 – 4 March 2010 PRAGMA 18, San Diego Nornisah Mohamed, USM

Hierarchical Map Reduce (HMR) Application: AutoDock Virtual Screening Yuan Luo, IU

Karma Provenance System and Applications

Benchmarks Technology adopted and improved, Biosciences WG Rocks and virtualization gLite, globus Data turbine Duckling portal Social networks? Gfarm Workflow systems CSF4 Amazone EC2 Network? TDW, SAGE Opal 2, Opal OP