NDM-1+Beta-lactamase+Project

a.k.a. CRE (Carbapenem-Resistant Enterobacteriaceae)

Dr. B notes (090613) Wet Lab stuff: Nitrocefin is in. (2 vials of 5mg each) - standard curve of varying amount of enzyme - determine Km & kinetics

-- find remote desktop in Windows start menu from your computer and enter this info. vdsstationpc.dyndns.org username: vdsstationPC\vdsclass passwerd: same as to get into laptops in lab
 * Graphpad prism** login info (remote desktop using Windows - not sure if it will work from a Mac or Linux)

Alternatively, this is the computer outside of Dr. B’s office that you can go sit at.

Virtual Stuff

VS4 Redo Protocol (version 3)

 * See:** GDocs/Protocols/VirtualScreening/...

re-run the docking with the modifications made (if you didn't originally have a metal or a ligand - restart with a PDB structure that has a metal and a ligand in the active site) post results in table below alongside your original VS4 results

VS4 Redo Again Protocol
same as above, but this time Delete the CONECT records to the Zincs (or any metals) in your PDB file after it has gone through Molprobity

INSTRUCTIONS:

 * 1) Choose which structure you will dock against. Fill in your name next to that entry. Only 5 researchers per target.
 * 2) Once you have completed docking, enter your results in Table 2. below.

DE La O || James T. || Alakh R || Jessica N. || Katherine V. ||
 * Table 1**. Associated PDB entries of crystal structures for NDM-1 beta-metallo lactamase
 * ~ PDB ID: ||~ Description ||~ Researcher 1 ||~ Researcher 2 ||~ Researcher 3 ||~ Researcher 4 ||~ Researcher 5 ||
 * 4HKY || New Delhi Metallo-beta-Lactamase-1, Complexed with Cd and Faropenem || Alice C. || Qasim A. || Marianna U. || Miguel T. || Brandy C. ||
 * 4HL1 || Crystal Structure of New Delhi Metallo-beta-Lactamase-1, Complexed with Cd and Ampicillin || Aaron H. || Grant T. || Jensen G. || Grayson N. || Spencer C. ||
 * 4HL2 || New Delhi Metallo-beta-Lactamase-1 1.05 A structure Complexed with Hydrolyzed Ampicillin (Metals were shown in PyMol, but not in GOLD) || Julia C. || Karuna A. || Jacqueline E. || Gabe H. ||  ||
 * 4GYQ || Crystal Structure of New Delhi Metallo-beta-Lactamase-1 D223A mutant from Klebsiella pneumoniae- ||  ||   ||   ||   ||   ||
 * 4GYU || Crystal Structure of New Delhi Metallo-beta-Lactamase-1 A121F mutant from Klebsiella pneumoniae- ||  ||   ||   ||   ||   ||
 * 4H0D || New Delhi Metallo-beta-Lactamase-1 Complexed with Mn from Klebsiella pneumoniae ||  ||   ||   ||   ||   ||
 * 4EYB || Crystal structure of NDM-1 bound to hydrolyzed oxacillin || Caroline C. || D'Ondria P. || Kevin E. || Shannon R. || William I. ||
 * 4EXS || Crystal structure of NDM-1 bound to L-captopril || Gautam W. || Khady D. || William E. || Nicole W. || Brendan C. ||
 * 4EXY || Crystal structure of NDM-1 bound to ethylene glycol || Emily J. || Nancy I. || Alyssa K. || Vicky G. || Hyun-Young L. ||
 * 4EY2 || Crystal structure of NDM-1 bound to hydrolyzed methicillin || Tony G. || Karinna L. || Melissa H. || Dax F.G. || Ramiro R. ||
 * 4EYF || Crystal structure of NDM-1 bound to hydrolyzed benzylpenicillin || Imran Zafar || Feng G. || Grace T. || Daniel D. || Nicolet F. ||
 * 4EYL || Crystal structure of NDM-1 bound to hydrolyzed meropenem || Priya P. || Jiaqi Z. || Stella M. || Selena I. || Renee F. ||
 * 3PG4 || The crystal structure of New Delhi Metallo-beta lactamase (NDM-1) ||  ||   ||   ||   ||   ||
 * 3SPU || apo NDM-1 Crystal Structure- ||  ||   ||   ||   ||   ||
 * 3SRX || New Delhi Metallo-beta-Lactamase-1 Complexed with Cd- ||  ||   ||   ||   ||   ||
 * 3SBL || Crystal Structure of New Delhi Metal-beta-lactamase-1 from Klebsiella pneumoniae || Jesus
 * 3SFP |||| Crystal Structure of the Mono-Zinc-boundform of New Delhi Metallo-beta-Lactamase-1 from Klebsiella pneumoniae ||  ||   ||   ||   ||
 * 3ZR9 || STRUCTURE OF NEW DELHI METALLO-BETA-LACTAMASE 1 (NDM-1)- ||  ||   ||   ||   ||   ||
 * 3S0Z || Crystal structure of New Delhi Metallo-beta-lactamase (NDM-1)- ||  ||   ||   ||   ||   ||
 * 3Q6X || Crystal structure of NDM-1 in complex with hydrolyzed ampicillin || Shivani B. || Serena Z. || Shawn O || So-Youn P || Anita V. ||
 * 3RKJ || Crystal Structure of New Delhi Metallo-Beta-Lactamase-1 from Klebsiella pnueumoniae (no metal in active site- could not re-run VS4) || Keely W. || Aditi S. || Kavya K. || Min S. || Ariel C. ||
 * 3RKK || Crystal Structure of New Delhi Metallo-Beta-Lactamase-1 from Klebsiella pneumoniae- || __#|Seo__ Kelly K. ||  ||   ||   ||   ||

-drug ||~ Penicillin -drug ||~ Clavulanic Acid -inhibitor ||~ Aspririn -random ||~ Original Ligand ||~ ' (REDO redo) POSITIVE' CTRL1 ||~ (REDO redo) Faropenem -drug ||~ (REDO redo) Penicillin -drug ||~ (REDO redo) Clavulanic Acid -inhibitor ||~ (REDO redo) Aspririn -random ||~ (REDO redo) Original Ligand ||
 * Table 2**. Gold docking scores of various ligands against NDM-1 beta-metallo lactamase crystal sctructures (nonhis)
 * ~ # ||~ RESEARCHER NAME ||~ PDB ID ||~ 'POSITIVE' CTRL1 ||~ Faropenem
 * 1 || Gautam W. || 4EXS || 79.39 || 57.05 || 70.08 || 52.21 || 50.05 || 48.55 ||  ||   ||   ||   ||   ||   ||
 * 2 || Khady D. || 4EXS || 64.47 || 73.75 || 83.51 || 72.77 || 68.75 || 69.83 ||  ||   ||   ||   ||   ||   ||
 * 3 || Nicole W. || 4EXS || 64.83 || 72.19 || 84.14 || 70.06 || 68.48 || 69.07 ||  ||   ||   ||   ||   ||   ||
 * 4 || Jesus De || 3SBL || 49.51 || 45.79 || 42.19 || 44.91 || 40.97 || 43.99 ||  ||   ||   ||   ||   ||   ||
 * 5 || Tony G. || 4EY2 || 74.86 || 77.57 || 70.23 || 65.34 || 68.7 || 80.27 || 79.27 || 81.04 || 74.00 || 70.93 || 65.83 || 84.15 ||
 * 6 || Shivani B. || 3Q6X || 80.35 || 80.70 || 76.71 || 67.52 || 69.72 || 83.38 ||  ||   ||   ||   ||   ||   ||
 * 7 || Serena Z. || 3Q6X || 80.50 || 81.35 || 76.42 || 67.86 || 69.90 || 84.17 ||  ||   ||   ||   ||   ||   ||
 * 8 || Shawn O. || 3Q6X || 80.44 || 81.57 || 77.31 || 67.78 || 72.22 || 83.26 ||  ||   ||   ||   ||   ||   ||
 * 9 || William E. || 4EXS || 64.56 || 58.59 || 70.18 || 53.04 || 50.03 || 49.58 ||  ||   ||   ||   ||   ||   ||
 * 10 || Imran Zafar || 4EYF || 76.66 || 77.18 || 72.53 || 64.4 || 67.15 || 81.4 ||  ||   ||   ||   ||   ||   ||
 * 11 || Caroline C. || 4EYB || 74.96 || 78.48 || 70.76 || 64.27 || 67.00 || 92.86 ||  ||   ||   ||   ||   ||   ||
 * 12 || Alice C. || 4HKY || 86.22 || 74.46 || 76.00 || 66.42 || 67.47 || 77.17 ||  ||   ||   ||   ||   ||   ||
 * 13 || Keely W. || 3RKJ || 60.2 || 42.1 || 49.6 || 36.2 || 34.9 || 10.7 ||  ||   ||   ||   ||   ||   ||
 * 14 || Grace T. || 4EYF || 75.67 || 76.81 || 72.89 || 64.67 || 67.19 || 83.91 ||  ||   ||   ||   ||   ||   ||
 * 15 || Kavya K. || 3RKJ || 62.44 || 41.00 || 50.69 || 37.24 || 35.31 || 11.45 || (no metal in active site- could not re-run VS4) || NA || NA || NA || NA || NA ||
 * 16 || Aaron Hong || 4HL1 || 53.95 || 81.18 || 62.39 || 73.67 || 75.92 || 83.60 ||  ||   ||   ||   ||   ||   ||
 * 17 || D'Ondria P. || 4EYB || 77.48 || 88.22 || 80.07 || 70.88 || 70.65 || 84.19 ||  ||   ||   ||   ||   ||   ||
 * 18 || Nicolet F. || 4EYF || 73.29 || 80.40 || 76.36 || 65.64 || 69.17 || 81.00 || 71.96 || 84.50 || 79.23 || 70.53 || 80.28 || 83.34 ||
 * 19 || Grayson N. || 4HL1 || 61.99 || 83.43 || 77.54 || 75.55 || 75.66 || 83.95 ||  ||   ||   ||   ||   ||   ||
 * 20 || Emily J. || 4EXY || 79.94 || 74.34 || 70.79 || 74.22 || 73.29 || 38.68 ||  ||   ||   ||   ||   ||   ||
 * 21 || Katherine V. || 3SBL || 45.23 || 43.29 || 41.76 || 44.03 || 41.26 || 44.41 || 48.70 || 42.78 || 42.78 || 45.21 || 41.33 || 44.95 ||
 * 22 || Marianna U. || 4HKY ||  ||   ||   ||   ||   ||   ||   ||   ||   ||   ||   ||   ||
 * 23 || Jessica N. || 3SBL || 44.69 || 46.04 || 42.63 || 44.92 || 41.33 || 44.37 ||  ||   ||   ||   ||   ||   ||
 * 24 || Karinna L. || 4EY2 || 77.44 || 78.61 || 69.95 || 65.41 || 68.54 || 78.45 ||  ||   ||   ||   ||   ||   ||
 * 25 || Grant T. || 4DHL1 || 87.93 || 81.35 || 79.90 || 75.43 || 75.63 || 87.95 ||  ||   ||   ||   ||   ||   ||
 * 26 || Kevin E. || 4EYB || 75.66 || 77.78 || 71.10 || 64.73 || 67.30 || 89.56 || 80.93 || 80.38 || 76.66 || 69.89 || 69.62 || 87.91 ||
 * 27 || Alyssa K. || 4EXY || 74.16 || 74.96 || 70.23 || 74.46 || 73.41 || 38.78 || 81.32 || 77.09 || 73.95 || 73.74 || 73.76 || 41.37 ||
 * 28 || Aditi S. || 3RKJ || 67.72 || 57.63 || 61.38 || 55.15 || 48.43 || 23.76 ||  ||   ||   ||   ||   ||   ||
 * 29 || Qasim A. || 4HKY || 49.43 || 75.32 || 73.16 || 65.18 || 67.27 || 69.1 ||  ||   ||   ||   ||   ||   ||
 * 30 || Julia C. || 4HL2 || 79.93 || 80.14 || 79.46 || 69.94 || 66.06 || 82.59 ||  ||   ||   ||   ||   ||   ||
 * 31 || Feng G. || 4EYF || 74.74 || 79.93 || 76.12 || 65.54 || 69.33 || 83.12 ||  ||   ||   ||   ||   ||   ||
 * 32 || Min S. || 3RKJ || 65.13 || 55.55 || 52.15 || 51.48 || 43.23 || 25.23 ||  ||   ||   ||   ||   ||   ||
 * 33 || Melissa H. || 4EY2 || 74.67 || 79.04 || 70.34 || 65.31 || 65.98 || 78.62 || 78.73 || 84.20 || 77.53 || 70.16 || 71.03 || 84.68 ||
 * 34 || Shannon R. || 4EYB || 76.96 || 76.40 || 75.45 || 64.53 || 67.12 || 91.53 ||  ||   ||   ||   ||   ||   ||
 * 35 || Anita V. || 3Q6X || 75.69 || 53.73 || 50.68 || 35.44 || 36.04 || 58.87 ||  ||   ||   ||   ||   ||   ||
 * 36 || Marianna U. || 4HKY || 74.5 || 74.34 || 70.53 || 60.82 || 62.7 || 69.61 ||  ||   ||   ||   ||   ||   ||
 * 37 || Miguel T. || 4HKY || 85.28 || 62.88 || 59.27 || 50.21 || 50.64 || 59.21 ||  ||   ||   ||   ||   ||   ||
 * 38 || Seo Kelly K. || 3RKK || 8.73 || 26.09 || 29.38 || 21.15 || 21.97 || 11.93 ||  ||   ||   ||   ||   ||   ||
 * 39 || Ramiro R. || 4EY2 || 74.06 || 76.91 || 70.46 || 65.41 || 67.96 || 69.15 ||  ||   ||   ||   ||   ||   ||
 * 40 || Priya P. || 4EYL || 73.73 || 82.76 || 82.54 || 72.63 || 73.77 || 91.35 || 81.51 || 85.92 || 84.55 || 74.62 || 74.79 || 97.04 ||
 * 41 || So-Youn P. || 3Q6X || 80.43 || 81.96 || 77.29 || 67.84 || 69.82 || 82.84 ||  ||   ||   ||   ||   ||   ||
 * 42 || Daniel D. || 4EYF || 73.27 || 77.73 || 73.06 || 64.84 || 66.86 || 82.29 ||  ||   ||   ||   ||   ||   ||
 * 43 || Nancy I. || 4EXY || 78.89 || 75.23 || 70.63 || 73.48 || 74.21 || 38.53 ||  ||   ||   ||   ||   ||   ||
 * 44 || Ariel C. || 3RKJ || 53.40 || 35.98 || 41.54 || 29.62 || 32.46 || 25.60 ||  ||   ||   ||   ||   ||   ||
 * 45 || Vicky G. || 4EXY || 78.5 || 73.07 || 68.09 || 72.83 || 73.81 || 38.24 || 85.78 || 76.31 || 71.19 || 72.99 || 73.28 || 40.03 ||
 * 46 || Spencer C. || 4HL1 || 72.79 || 83.29 || 83.08 || 75.30 || 77.52 || 69.16 ||  ||   ||   ||   ||   ||   ||
 * 47 || Stella M. || 4EYL || 75.28 || 83.23 || 83.07 || 73.62 || 73.58 || 105.56 ||  ||   ||   ||   ||   ||   ||
 * 48 || Jiaqi Z. || 4EYL || 76.58 || 83.05 || 82.59 || 73.95 || 72.76 || 92.26 ||  ||   ||   ||   ||   ||   ||
 * 49 || Hyun-Young L. || 4EXY || 80.07 || 74.45 || 71.16 || 74.41 || 74.09 || 38.87 ||  ||   ||   ||   ||   ||   ||
 * 50 || Selena I. || 4EYL || 75.05 || 82.23 || 82.79 || 72.63 || 74.18 || 91.82 ||  ||   ||   ||   ||   ||   ||
 * 51 || Brandy C. || 4HKY || 85.79 || 74.99 || 68.49 || 65.52 || 65.71 || 67.37 ||  ||   ||   ||   ||   ||   ||
 * 52 || Renee F. || 4EYL || 75.26 || 66.35 || 68.88 || 54.87 || 56.67 || 58.53 || 84.34 || 69.26 || 71.12 || 59.02 || 59.95 || N/A ||
 * 53 || James T. || 3SBl || 44.94 || 46.21 || 40.56 || 44.79 || 40.98 || 45.75 ||  ||   ||   ||   ||   ||   ||
 * 54 || Karuna A. || 4HL2 || 73.33 || 71.9 || 88.7 || 87.9 || 92.23 || 79.45 ||  ||   ||   ||   ||   ||   ||
 * 55 || Jacqueline E. || 4HL2 || 67.91 || 52.52 || 59.76 || 38.11 || 37.55 || 63.49 || 67.76 || 52.56 || 59.85 || 41.66 || 35.80 || 63.84 ||
 * 56 || Kevin E. (redo) || 4EYB || 80.93 || 80.38 || 76.66 || 69.89 || 69.62 || 87.91 ||  ||   ||   ||   ||   ||   ||
 * 57 || Katherine V. (redo) || 3SBL || 48.70 || 42.78 || 42.78 || 45.21 || 41.33 || 44.95 ||  ||   ||   ||   ||   ||   ||
 * 58 || Gabe H. || 4HL2 || 115.04 || 80.56 || 76.95 || 65.54 || 66.96 || 86.35 || 113.25 || 85.00 || 68.53 || 70.53 || 69.24 || 91.88 ||
 * 59 || Brian C. || 3Q6X || 80.26 || 59.67 || 76.41 || 67.67 || 70.41 || 82.39 ||  ||   ||   ||   ||   ||   ||
 * 60 || Salil D. || 4EYB || 77.28 || 78.37 || 70.60 || 66.56 || 67.08 || 80.15 ||  ||   ||   ||   ||   ||   ||

Binding DB Info: (To Be Done)
@http://www.bindingdb.org/bind/index.jsp search for "Metallo-beta-lactamase"

Download Binding DB compounds using the '**Computed 3D by [| Vconf] -m prep**' option (Does not work)

REFERENCES:
[|An altered zinc-binding site confers resistance to a covalent inactivator of New Delhi metallo-beta-lactamase-1 (NDM-1) discovered by high-throughput screening.] Thomas PW, Spicer T, Cammarata M, Brodbelt JS, Hodder P, Fast W. Bioorg Med Chem. 2013 Mar 29. doi:pii: S0968-0896(13)00245-9. 10.1016/j.bmc.2013.03.031. [Epub ahead of print] PMID: 23591260

[|Characterization of purified New Delhi metallo-β-lactamase-1.] Thomas PW, Zheng M, Wu S, Guo H, Liu D, Xu D, Fast W. Biochemistry. 2011 Nov 22;50(46):10102-13. doi: 10.1021/bi201449r. Epub 2011 Nov 1. PMID: 22029287 [|Related citations] [|Remove from clipboard] Kim, Y., Cunningham, M. A., Mire, J., Tesar, C., Sacchettini, J. & Joachimiak, A. NDM-1, the ultimate promiscuous enzyme: substrate recognition and catalytic mechanism. FASEB J. 27, Epub ahead of print (2013). King, D. T., Worrall, L. J., Gruninger, R. & Strynadka, N. C. J. New Delhi metallo-β- lactamase: structural insights into β-lactam recognition and inhibition. JACS 134, 11362-11365 (2012).

Metallo Beta-Lactamase GOLD docking paper (NOT New Delhi version though) - 071613 JTB http://www.ncbi.nlm.nih.gov/pubmed/16378729