1	HIV 2-D & 3-D Integrated Structural Database T. N. Bhat National Institute of Standards and Technology Gaithersburg MD 20899-8314
2	HIV Structural Database, an Integrated Resource Of 2-D And 3-D Structures HIVPR presents one of the most successful stories of structure-based drug design (indinavir, ritonavir, saquinavir, nelfinavir) Lots of successful and not so successful stories exist All stories are very important, successful or not Often, particularly in an industrial set up, resources are hard to justify to publish and to deposit structural data of not so successful results Unlike for 3-D structures, no established public archival facility exists for 2-D structural data Existing web resources for 2-D and 3-D data are not integrated For this reason, NIST, in collaboration with NCI and NIAID initiated an effort to setup a special archival and distribution system for HIVPR 2-D and 3-D structures
3	What Has Been Done So Far HIVSDB has a SQL based dynamic, customizable webpage for 2-D and 3-D structures in an integrated environment HIVSDB has about 70% more HIV protease 3-D structures than in the PDB HIVSDB has about 500 active HIV Protease inhibitor 2-D structures Dynamic links to biological, chemical and drug-resistance data at NIAID and at NCBI are provided HVSDB uses a novel query tool to search abstract, drugs, inhibitors, authors, company, and more,.. Abstract, citation, author, journal, year, pages,.. Inhibitor, IUPAC name, fragment name, .. Mutation, crystal growth, 2-D drawings.. Space group, unit cell,..
4	Main Page of HIVSDB
5	Inhibitor Search Using a Data-tree Often we imagine compounds using chemical definitions such as ring structures, sulfur containing compounds, and we visualize their structures in terms of 2-D drawings Chemical data-tree is handy for formulating such imaginations Will not it be nice to query a database using such definitions based on data-tree? Yes Will not it be nice to express our imagination into a web query using 2-D drawings? Yes For this reason in HIVSDB All compounds were annotated into a data-tree Tools are developed to step through and query the data-tree using both text and 2-D drawings A novel method called Chem-BLAST is developed to look for related chemical structures using a method analogous to that of the popular BLAST program used for sequence comparisons
6	The Chem-Blast (Chemical Block Layered Alignment of Structure Technique, Prasanna et al. 2005) BLAST Program has been very successful in querying & comparing protein/DNA sequences Chem-BLAST provides similar functionality for chemical compounds using chemical layers such as those of fragments, subgroups and classes Chem-BLAST compares structures using the different layers of a data-tree that relates all compounds in the database While searching for similar structures, layered approach of Chem-BLAST facilitates zooming in & out of structural features using the definitions made in different layers of the data-tree
7	Data-tree
8	Concept of Chem-BLAST
9	Query of Inhibitors Using Text Strings
10	Advanced Text Query Queries using a single string often produce too many hits Therefore, in HIVSDB a query may be refined using AND or OR Each query result is piped into several tools to aid new queries
11	Chemical Motif Search Either by Text Stings or by 2-D Drawings Often we conceptualize questions using more than one selection criteria for the compound Often we look for a structural motif ; anything-something-anything-something-anything-something In HIVSDB, one may use AND or OR to join query concepts specified using text or 2-D drawings Concepts may be joined explicitly in a text box or implicitly by the selection of a 2-D drawing
12	Query of Inhibitors Using 2-D Drawings vs. Using IUPAC Names In HIVSDB, any and every query may be done using 2-D drawings IUPAC names are hard to remember At times IUPAC names run into several lines In many databases, annotation of drugs using IUPAC names is done for annotators convenience since names may be generated using batch process and such annotation is not best for customers to specify a query Because of their length and complexity, IUPAC names are more suited for indexing drugs in computers than for specifying drugs by users in queries I do not often see people using IUPAC names to specify a complete compound in a conversation, then, how can I expect a user to type in IUPAC name into a query box? Instead of IUPAC names, 2-D drawings of functional fragments are a better alternative for customers to identify compounds of his/her interest during a query. Therefore, in HIVSDB we focus on annotation and query using 2-D drawings – the language we use to conceptualize probes for queries
13	Fragment-Chem-BLAST
14	Specification of Multiple Fragments For Chem-BLAST
15	Chem-BLAST Zooming-in or Zooming-out of Compounds
16	Query on Identical Inhibitors Using InChI
17	Interactive Visual Tools to Study Enzyme Drug Interactions
18	Indexing of Compounds And Its Fragments in HIVSDB Using IUPAC International Chemical Identifier (InChI) http://www.iupac.org/projects/2000/2000-025-1-800.html
19	Assignment of InChI to PDB Structures
20	Download of Structural Data In HIVSDB all queries allow one to download PDB, mol or 2-D drawings
21	Acknowledgements M.D.Prasanna A.Wlodawer (NCI) M. Nasr (NIAID) J.Vondrasek H. Rodriguez R. Goldberg