Computer-aided Molecular Design - Yuan-Ping Pang

Protein Structure Prediction

Pro-apoptotic proteins with the BH3-binding groove occupied by BH3-only proteins

Model of Bak in complex with the BH3 domain of Noxa (Noxa and Bak complex or Noxa•Bak complex)

• Model of an average conformation without energy minimization
• Model of an average conformation with energy minimization
• Model of an instantaneous conformation with bound water

Related article

• Dai H, Smith A, Meng XW, Schneider PA, Pang YP, Kaufmann SH. Transient binding of an activator BH3 domain to the Bak BH3-binding groove initiates Bak oligomerization, J. Cell Biol., 194, 39-48 (2011).

Botulinum neurotoxin serotype A endopeptidase in complex with a small-molecule inhibitor HAB

Models (released March 5, 2010)

• Model 1
• Model 2
• Model 3

HAB has a highly flexible functional group; the percentages of the top three most-populated conformations of HAB in Models 1, 2 and 3 are, respectively, 21 percent, 13 percent and 12 percent. Only 33 percent of the heavy atoms of HAB are provided in the released models. The full structure of HAB will be released upon manuscript acceptance. Read more about HAB.

Related articles

• Pang YP, Vummenthala A, Mishra RK, Park JG, Wang S, Davis J, Millard CB, Schmidt JJ. Potent new small-molecule inhibitor of botulinum neurotoxin serotype A endopeptidase developed by synthesis-based computer-aided molecular design. PLoS One. 2009 Nov 10;4(11):e7730. PMID: 19901994
• Tang J, Park JG, Millard CB, Schmidt JJ, Pang YP. Computer-aided lead optimization: Improved small-molecule inhibitor of the zinc endopeptidase of botulinum neurotoxin serotype A. PLoS One. 2007 Aug 22;2(1):e761. PMID: 17712409
• Park JG, Sill PC, Makiyi EF, Garcia-Sosa AT, Millard CB, Schmidt JJ, Pang YP. Serotype-selective, small-molecule inhibitors of the zinc endopeptidase of botulinum neurotoxin serotype A. Bioorg Med Chem. 2006 Jan 15;14(2):395-408. PMID: 16203152

African malaria mosquito acetylcholinesterase

Model (released Dec. 12, 2009)

• Model of an inhibitor-bound acetylcholinesterase of Anopheles gambiae sensu stricto (AP-AgAChE)

AP-AgAChE contains a free cysteine at the opening of the active-site gorge of an acetylcholinesterase of the African malaria mosquito and is paralogous to the acetylcholinesterase of Drosophila melanogaster; the inhibitor structure of AP-AgAChE will be released upon manuscript acceptance. Read more about African malaria mosquito acetylcholinesterase.

Related articles

• Pang YP. Novel acetylcholinesterase target site for malaria mosquito control. PLoS One. 2006 Dec 20;1:e58. PMID: 17183688
• Pang YP, Singh SK, Gao Y, Lassiter TL, Mishra RK, Zhu KY, Brimijoin S. Selective and irreversible inhibitors of aphid acetylcholinesterases: Steps toward human-safe insecticides. PLoS One. 2009;4(2):e4349. PMID: 19194505
• Pang YP, Ekstrom F, Polsinelli GA, Gao Y, Rana S, Hua DH, Andersson B, Andersson PO, Peng L, Singh SK, Mishra RK, Zhu KY, Fallon AM, Ragsdale DW, Brimijoin S. Selective and irreversible inhibitors of mosquito acetylcholinesterases for controlling malaria and other mosquito-borne diseases. PLoS One. 2009 Aug 28;4(8):e6851. PMID: 19714254