Willy Wriggers and Klaus Schulten. Stability and dynamics of G-actin: Back door water diffusion and behavior of a subdomain 3/4 loop. Biophysical Journal, 73:624-639, 1997.

Molecular Dynamics simulations have been performed on solvated G-actin bound to ADP and ATP, starting with the crystal structure of the actin-DNase 1 complex, including a Ca2+ or Mg2+ ion at the high-affinity divalent cation binding site. Water molecules have been found to enter the nucleotide binding site (phosphate vicinity) along two pathways, from the side where the nucleotide base is exposed to water, as well as from the opposite side. The water channels suggest a ``back door'' mechanism for ATP hydrolysis in which the phosphate is released to a side opposite to that of nucleotide binding and unbinding. The simulations reveal also a propensity of G-actin to alter its crystallographic structure towards the filamentous structure. Domain movement closes the nucleotide cleft, the movement being more pronounced for bound Mg2+. The conformational change is interpreted as a response of the system to missing water molecules in the crystal structure. The structures arising in the simulations, classified according to nucleotide cleft separation and radius of gyration of the protein, fall into two distinct clusters: a cluster of states which are similar to the G-actin crystal structure and a cluster of states with small cleft separation and with the subdomain 3/4 loop 264-273 detached from the protein. The latter states resemble the filamentous structure, in which the loop connects the two strands of the actin filament.

[Article PDF] [Nucleotide Parameters]

Main Page