Origins of the high affinity binding of the biotin-(strept)avidin complex

COMP 235

Jason DeChancie, jdechanc@chem.ucla.edu, Department of Chemistry and Biochemistry, UCLA, 607 Charles E. Young Drive East, Los Angeles, CA 90095-1596 and K. N. Houk, houk@chem.ucla.edu, Department of Chemistry and Biochemistry, University of California, 405 Hilgard Ave, Los Angeles, CA 90095-1569.
DFT and MP2 calculations employing model systems for the (strept)avidin binding site involving the hydrogen bonding and hydrophobic residues to the ureido moiety of biotin have been carried out. Biotin is predicted to be significantly polarized in the binding site. Cooperative hydrogen bonding enhances binding compared to individual interactions. Aspartic acid is the key residue stabilizing the hydrogen bonding network. Aspartic acid is directly hydrogen bonded with biotin in streptavidin and is one residue removed in avidin, and the latter is surprisingly more favorable. This work is an advancement towards the answer to a long lasting question: Why are the majority of protein-ligand interactions so poor in comparison to the biotin-(strept)avidin complex?
 

Poster Session -- Sponsored by Novartis Institutes for BioMedical Research
6:00 PM-8:00 PM, Tuesday, 30 August 2005 Washington DC Convention Center -- Hall A, Poster

Division of Computers in Chemistry

The 230th ACS National Meeting, in Washington, DC, Aug 28-Sept 1, 2005