N. Vaidehi et Wa. Goddard, Domain motions in phosphoglycerate kinase using hierarchical NEIMO molecular dynamics simulations, J PHYS CH A, 104(11), 2000, pp. 2375-2383
We examined the large-scale domain motions in the glycolytic enzyme phospho
glycerate kinase (PGK) using the hierarchical Newton-Euler inverse mass ope
rator (H-NEIMO) molecular dynamics (MD) method. NEIMO is an efficient MD me
thod for torsion-only internal coordinate dynamics method. H-NEIMO is an ex
tension of the NEIMO method for doing coarse grain MD in which large domain
s of a protein are treated as rigid clusters connected by flexible torsion
angles. This allows an efficient examination of the low-frequency long time
scale motions. We find that with both substrates bound (Phospho glycerate
and ATP) on PGK the closed domain structure is more stable than the open do
main structure. During the H-NEIMO MD the two domains of the open structure
come close together while the N-terminus of helix 14 (namely, Gly-394 in t
he R65Q yeast structure) moves close to the ATP derivative, suggesting that
it could be involved in the mechanism of phosphoryl transfer. We find that
residues 175-183 in the R65Q yeast ternary complex structure are important
in triggering the closure of the domains, resulting in a piston-like motio
n of helix 7. The domain rotation axis in the all atom Cartesian MD simulat
ions is close to that of H-NEIMO MD. The axis of domain rotation in H-NEIMO
is also in the same region as the rotation axis between two experimental c
rystal structures. Thus, H-NEIMO captures the long time scale motions in ra
ther short simulation times. This demonstrates that H-NEIMO is a promising
mesoscale coarse grain molecular dynamics technique to determine the low-fr
equency long time motions responsible for the function of proteins such as
PGK.