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

COMP 257

Bing Wang, bwang@qtp.ufl.edu, Xiao He, thomas8121@gmail.com, and Kenneth M. Merz Jr., merz@qtp.ufl.edu. 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