Probing protein-ligand interactions by ab initio NMR chemical shift calculations

COMP 257

Bing Wang,, Xiao He,, and Kenneth M. Merz Jr., Department of Chemistry and The Quantum Theory Project, University of Florida, P.O Box 118435, Gainesville, FL 32611-8435
We have developed an automatic fragmentation quantum mechanics/molecular mechanics (AF-QM/MM) approach to routinely calculate NMR chemical shifts for biological systems. This approach shows excellent agreement with full system calculations as tested on a small protein Trpcage. We have applied this approach to study the FKBP-GPI complex. Good agreement between our calculated ligand proton chemical shifts with experiment was obtained for ten NMR structures, but not for the decoy poses. Therefore, CSP RMSD offers a straightforward measurement for scoring different poses. Our results have demonstrated that the comparisons of ab initio/DFT NMR chemical shifts with experimental values can provide insights into protein-ligand interactions at the molecular level. The AF-QM/MM approach has potential applications in the structure-based drug discovery process such as SAR by NMR.

Poster Session
6:00 PM-8:00 PM, Tuesday, August 18, 2009 Walter E. Washington Convention Center -- Ballroom A, Poster

Division of Computers in Chemistry

The 238th ACS National Meeting, Washington, DC, August 16-20, 2009