Achievement

COB student David Rooklin and lab leader Y. Zhang have applied ab initio QM/MM MD simulations to investigate a recently discovered human apyrase enzyme, human soluble calcium-activated nucleotidase-1 which has been the focus of experimental protein design efforts and has potential therapeutic applications against harmful blood clotting. Their study is the first detailed computational mechanistic work on this unique class of phosphoryl transfer enzymes. They discovered a calcium binding site, characterized an original reactant complex, and determined a detailed nucliotidase reaction mechanism. This mechanistic work is important to the understanding of this ubiquitous biochemical reaction, and sheds light on certain limitations to the force fields currently adopted for this type of phosphoryl molecular modeling. We are now working to improve these tools using a force matching method in conjunction with accurate QM/MM data from condensed phase systems.