1 / 33

PDB Research Experience Summer Intern Presentation July 14, 2009 Heidi Chen Jane Hand Mira Patel

PDB Research Experience Summer Intern Presentation July 14, 2009 Heidi Chen Jane Hand Mira Patel Mike Ticchio. Outline. Projects & Goals Peptide Reference Dictionary Antibiotics Examples Inhibitors Second Life Future. Projects & Goals. Peptide Reference Dictionary

tanek
Download Presentation

PDB Research Experience Summer Intern Presentation July 14, 2009 Heidi Chen Jane Hand Mira Patel

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. PDB Research Experience • Summer Intern Presentation • July 14, 2009 • Heidi Chen • Jane Hand • Mira Patel • Mike Ticchio

  2. Outline • Projects & Goals • Peptide Reference Dictionary • Antibiotics • Examples • Inhibitors • Second Life • Future

  3. Projects & Goals • Peptide Reference Dictionary • Gather info for a searchable dictionary • Organize information about antibiotics and inhibitors from various databases • Second Life • Incorporate ”Molecule of the Month” into Second Life

  4. Antibiotics • Given a list from Miri (EBI) • 45 antibiotics + PDB instances • expanded the list to 73 antibiotics • analyzed a total of 163 PDB instances

  5. wwPDB Antibiotics List

  6. Antibiotics Spreadsheet A

  7. Databases SciFinder MeSH Merck Belstein KEGG Drugbank • Uniprot • PubChem • ChemSpider • chEBI • chemDB • ChemBank • Norine • ABX Guide • Bactibase • Novel Antibiotics

  8. What we found.. CAS Registry Number various IDS (KEGG, PubChem, etc.) synonyms functions Ontology (chEBI, KEGG Brite, MeSH) SMILES

  9. Antibiotics Spreadsheet B

  10. PDB Instances read primary citation record functions, often referencing other papers check for consistency between primary citation, PDB file, and other databases

  11. Issues PubChem multiple entries for the same compound no annotation ChemSpider could not search database with ChemSpider ID resolved

  12. Norine database for nonribosomal peptides provdes information about structure, function, taxonomy various links to PDB, Uniprot

  13. Norine

  14. Seqres of the PDB Entries DAPTOMYCIN 1t5m 1t5n : DKA TRP DSG ASP THR GLY ORN ASP DAL ASP GLY DSN MEG KYN 1xt7 : DKA TRP ASN ASP THR GLY ORN ASP DAL ASP GLY DSN LME KYN D-ASPARAGINE (R chirality) ASPARAGINE (S chirality) DSG vs. ASN

  15. Comparison of PDB Entries 1xt7 vs.1t5m, 1t5n R chirality 1xt7: V. Ramesh et al S chirality

  16. Seqres of the PDB Entries 1t5m 1t5n : DKA TRP DSG ASP THR GLY ORN ASP DAL ASP GLY DSN MEG KYN 1xt7: DKA TRP ASN ASP THR GLY ORN ASP DAL ASP GLY DSN LME KYN 2S,3S LME (3R)-3-METHYL-L-GLUTAMIC ACID MEG (2S,3R)-3-METHYL-GLUTAMIC ACID MEG vs. LME

  17. Comparison of PDB Entries 1xt7 vs.1t5m, 1t5n 3R chirality 1xt7: V. Ramesh et al

  18. Final Sequence of Daptomycin 1t5m 1t5n : DKA TRP DSG ASP THR GLY ORN ASP DAL ASP GLY DSN MEG KYN 1xt7: DKA TRP ASN ASP THR GLY ORN ASP DAL ASP GLY DSN LME KYN DKA TRP DSG ASP THR GLY ORN ASP DAL ASP GLY DSN LME KYN

  19. Balhimycin Comparison 1go6 KEGG C66H73Cl2N9O24 C66H75Cl2N9O25 1go6: G. Sheldrick et al

  20. What are these • antibiotics all about?

  21. Nisin • Type-A(I) Lantibiotic • Used in food as a preservative • Unusual AA's such as lanthionine, methyllanthionine, Dha, Dhb Asaduzzaman et. al

  22. Nisin • Traditional antibiotics have specific modes of action • Lantibiotics have more diverse modes of action • Binds lipid II and forms a stable pore • Inhibits in vitro lipid II synthesis Asaduzzaman et. al

  23. Nisin • Outlook on Nisin and other Lantibiotics • Has no known toxicity to humans • Works against vancomycin-resistant bacteria • In the preclinical stages of medical application • Threats of bioterrorism Asaduzzaman et. al

  24. What we're doing now... • Crosschecked each other's work • Started the first of two inhibitor/special peptide lists • combined vs. poly/split • 250 inhibitors with 394 PDB instances • Same format as antibiotics

  25. What we're doing now... • Chem Spider • CheBI • ChemDB • ChemBank • eMolecules • Inhibitor Source Book • Scifinder • MeSH • Merck • Beilstein • KEGG • DrugBank • PubChem

  26. What we're doing now... • Different approach to finding some CAS RNs • IUPAC names are difficult to search with • Can't use CAS RN to search in a few major databases • SMILEs don't work • Substructure search is possible

  27. Second Life • Created by Linden Labs • Virtual world to create a second life for yourself • Many uses • Education: Research/ Teaching/ Showcasing work • Embassies • Entertainment: Music/ Sports/ Art Exhibits/ Theater • Religion

  28. Second Life • Laboratory by Nature on the Elucian Islands • Meetings about ongoing various projects • Goal: Make interactive protein models • Highlight active sites and any residues of special interest • Test model: Myoglobin

  29. Second Life

  30. Second Life • Prims • Sculpties • Textures

  31. Continuing Second Life • Become more familiar with building in SL • Create an interactive molecule • Revamp and decorate our lab

  32. Timeline • June 1st – June 15th : Training • June 16th – July 1st : Antibiotics & Checking • July 2nd – end of July: Inhibitors & Checking • End of July – August 7th: Uncombined Inhibitors & Final Presentation

  33. Thanks! • Thanks to Dr. Helen Berman, Dr. Shuchi Dutta, Dr. Maggie Gabanyi, Hyunmi, and James • Questions?

More Related