12 research outputs found
Allosteric Transitions of Supramolecular Systems Explored by Network Models: Application to Chaperonin GroEL
Identification of pathways involved in the structural transitions of biomolecular
systems is often complicated by the transient nature of the conformations
visited across energy barriers and the multiplicity of paths accessible in the
multidimensional energy landscape. This task becomes even more challenging in
exploring molecular systems on the order of megadaltons. Coarse-grained models
that lend themselves to analytical solutions appear to be the only possible
means of approaching such cases. Motivated by the utility of elastic network
models for describing the collective dynamics of biomolecular systems and by the
growing theoretical and experimental evidence in support of the intrinsic
accessibility of functional substates, we introduce a new method,
adaptive anisotropic network model (aANM),
for exploring functional transitions. Application to bacterial chaperonin GroEL
and comparisons with experimental data, results from action minimization
algorithm, and previous simulations support the utility of aANM
as a computationally efficient, yet physically plausible, tool for unraveling
potential transition pathways sampled by large complexes/assemblies. An
important outcome is the assessment of the critical inter-residue interactions
formed/broken near the transition state(s), most of which involve conserved
residues