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Allosteric transitions of supramolecular systems explored by network models: application to chaperonin GroEL.

Yang Z, Májek P, Bahar I - PLoS Comput. Biol. (2009)

Bottom Line: Coarse-grained models that lend themselves to analytical solutions appear to be the only possible means of approaching such cases.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Computational Biology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

ABSTRACT
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.

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Evolution native contacts along the structural transition from R                                to R″ states.The number of intra-subunit (panel A) and inter-subunit (panel B)                                native contacts that are disrupted (upper panel) and formed (lower                                panel) vs. the reaction coordinate. The results                                refer to                                Fmin = 0.5                                for cis ring subunits along the transition from                                2C7E (R/T) to 1GRU (R″/R). Each bar represents the number                                of native contacts formed/broken at a given aANM                                iteration. Note the sharp increase near the energy barrier. See                                    Figure 10                                for the corresponding critical contacts.
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pcbi-1000360-g009: Evolution native contacts along the structural transition from R to R″ states.The number of intra-subunit (panel A) and inter-subunit (panel B) native contacts that are disrupted (upper panel) and formed (lower panel) vs. the reaction coordinate. The results refer to Fmin = 0.5 for cis ring subunits along the transition from 2C7E (R/T) to 1GRU (R″/R). Each bar represents the number of native contacts formed/broken at a given aANM iteration. Note the sharp increase near the energy barrier. See Figure 10 for the corresponding critical contacts.

Mentions: Figure 9A displays the time evolution of native contacts observed for a single subunit during the transition R→R″; and panel B shows its counterpart for inter-subunit contacts observed in the complex. Clearly, most of the native contacts remain unchanged throughout a large portion of the trajectory, while significant changes occur near the PTS, both with regard to the disruption (top panel) and formation (bottom panel) of contacts. Trajectories generated by varying aANM model parameters in the ranges 0.4<Fmin≤0.7 and 0.2≤Fmin≤0.5 yielded almost identical results, confirming the strong preference of the molecule to redistribute native contacts only in the vicinity of the PTS, while the large portions of the trajectories are enabled by minimal changes in native contacts. See also Figure S4 in the Supporting Information for the step R″→T.


Allosteric transitions of supramolecular systems explored by network models: application to chaperonin GroEL.

Yang Z, Májek P, Bahar I - PLoS Comput. Biol. (2009)

Evolution native contacts along the structural transition from R                                to R″ states.The number of intra-subunit (panel A) and inter-subunit (panel B)                                native contacts that are disrupted (upper panel) and formed (lower                                panel) vs. the reaction coordinate. The results                                refer to                                Fmin = 0.5                                for cis ring subunits along the transition from                                2C7E (R/T) to 1GRU (R″/R). Each bar represents the number                                of native contacts formed/broken at a given aANM                                iteration. Note the sharp increase near the energy barrier. See                                    Figure 10                                for the corresponding critical contacts.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2664929&req=5

pcbi-1000360-g009: Evolution native contacts along the structural transition from R to R″ states.The number of intra-subunit (panel A) and inter-subunit (panel B) native contacts that are disrupted (upper panel) and formed (lower panel) vs. the reaction coordinate. The results refer to Fmin = 0.5 for cis ring subunits along the transition from 2C7E (R/T) to 1GRU (R″/R). Each bar represents the number of native contacts formed/broken at a given aANM iteration. Note the sharp increase near the energy barrier. See Figure 10 for the corresponding critical contacts.
Mentions: Figure 9A displays the time evolution of native contacts observed for a single subunit during the transition R→R″; and panel B shows its counterpart for inter-subunit contacts observed in the complex. Clearly, most of the native contacts remain unchanged throughout a large portion of the trajectory, while significant changes occur near the PTS, both with regard to the disruption (top panel) and formation (bottom panel) of contacts. Trajectories generated by varying aANM model parameters in the ranges 0.4<Fmin≤0.7 and 0.2≤Fmin≤0.5 yielded almost identical results, confirming the strong preference of the molecule to redistribute native contacts only in the vicinity of the PTS, while the large portions of the trajectories are enabled by minimal changes in native contacts. See also Figure S4 in the Supporting Information for the step R″→T.

Bottom Line: Coarse-grained models that lend themselves to analytical solutions appear to be the only possible means of approaching such cases.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Computational Biology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

ABSTRACT
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.

Show MeSH