Structural Properties of the Closed Myosin Active Site During Equilibrium MD Simulations with Different Nucleotide Chemical States (ATP or ADP·P<i>_i</i>)

Abstract

<div><p>(A–D) Instantaneous distances between Mg²⁺ and oxygen atoms in its four nonwater ligands. (A) MM ATP state. (B) MM ADP·P<i>_i</i> state. (C) QM/MM ATP state. (D) QM/MM ADP·P<i>_i</i> state. O^1ß refers to O^1ß in ATP or ADP; O^1γ refers to O^1γ in ATP or the closest oxygen atom in P<i>_i</i>; O^Ser237 refers to O^γ in Ser237; O^Thr186 refers to O^γ2 in Thr186.</p><p>(E) Overlay of the active site in two snapshots from MM simulations with ATP and ADP·P<i>_i</i>, respectively. The one with color coding is for the ATP state while the one in grey is for the ADP·P<i>_i</i> state. The Mg²⁺-O^Ser237 distance is much longer in the ADP·P<i>_i</i>-state snapshot, due to displacements in both the Ser237 sidechain and the hydrolyzed nucleotide.</p><p>(F) Root mean square fluctuation (RMSF) for Cα atoms in the three critical active-site motifs based on equilibrium MM simulations. Ser237 has notably larger fluctuations in the ADP·P<i>_i</i> state, although the rest residues do not show distinct differences.</p></div