F. Pontiggia, A. Zen and C. Micheletti
Small and large scale conformational changes of adenylate
kinase: a molecular dynamics study of the subdomain motion and
mechanics
Biophys J 95. 5901
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Adenylate kinase (Adk), an enzyme which catalyzes the
phosphoryl transfer between ATP and AMP, can interconvert between the
open and catalytically-potent (closed) forms even without binding
ligands. Several aspects of the enzyme elasticity and internal
dynamics are analyzed here by atomistic molecular dynamics simulations
covering a total time span of 100ns. This duration is sufficiently long to reveal
a partial conversion of the enzyme which proceeds through jumps
between structurally-different substates. The intra- and
inter-substates contributions to the enzyme's structural fluctuations
are analyzed and compared both in magnitude and directionality. It is
found that, despite the structural heterogeneity of the visited
conformers, the generalized directions accounting for conformational
fluctuations within and across the substates are consistent and
can be described by a limited set of collective modes. The
functional-oriented nature of the consensus modes is suggested by
their good overlap with the deformation vector bridging the open
and closed crystal structures. The consistency of Adk's internal
dynamics over time-scales wide enough to capture intra-and
inter-substates fluctuations adds elements in favor of the recent
proposal that the free (apo) enzyme possesses an innate ability to
sustain the open/close conformational changes.