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Bridging between NMA and Elastic Network Models: Preserving All-Atom Accuracy in Coarse-Grained Models.

Na H, Jernigan RL, Song G - PLoS Comput. Biol. (2015)

Bottom Line: For this reason, coarse-grained models have been used successfully.The result is highly significant since it can provide descriptions of normal mode motions at an all-atom level of accuracy even for the largest biomolecular complexes.The application of our method to GroEL/GroES offers new insights into the mechanism of this biologically important chaperonin, such as that the conformational transitions of this protein complex in its functional cycle are even more strongly connected to the first few lowest frequency modes than with other coarse-grained models.

View Article: PubMed Central - PubMed

Affiliation: Department of Computer Science, Iowa State University, Ames, Iowa, United States of America.

ABSTRACT
Dynamics can provide deep insights into the functional mechanisms of proteins and protein complexes. For large protein complexes such as GroEL/GroES with more than 8,000 residues, obtaining a fine-grained all-atom description of its normal mode motions can be computationally prohibitive and is often unnecessary. For this reason, coarse-grained models have been used successfully. However, most existing coarse-grained models use extremely simple potentials to represent the interactions within the coarse-grained structures and as a result, the dynamics obtained for the coarse-grained structures may not always be fully realistic. There is a gap between the quality of the dynamics of the coarse-grained structures given by all-atom models and that by coarse-grained models. In this work, we resolve an important question in protein dynamics computations--how can we efficiently construct coarse-grained models whose description of the dynamics of the coarse-grained structures remains as accurate as that given by all-atom models? Our method takes advantage of the sparseness of the Hessian matrix and achieves a high efficiency with a novel iterative matrix projection approach. The result is highly significant since it can provide descriptions of normal mode motions at an all-atom level of accuracy even for the largest biomolecular complexes. The application of our method to GroEL/GroES offers new insights into the mechanism of this biologically important chaperonin, such as that the conformational transitions of this protein complex in its functional cycle are even more strongly connected to the first few lowest frequency modes than with other coarse-grained models.

No MeSH data available.


Cooperativity of residue motions using the first 15 lowest frequency modes of the coarse-grained ssNMA model.(A) The cooperativity within a single set of subunits: chain A from the cis ring, chain H from the trans ring, and chain O from GroES. (B) The cooperativity among all residue pairs in the GroEL/GroES complex.
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pcbi.1004542.g005: Cooperativity of residue motions using the first 15 lowest frequency modes of the coarse-grained ssNMA model.(A) The cooperativity within a single set of subunits: chain A from the cis ring, chain H from the trans ring, and chain O from GroES. (B) The cooperativity among all residue pairs in the GroEL/GroES complex.

Mentions: The motion correlation (or cooperativity) Ci,j between the i-th and j-th residues can be expressed as follows:Ci,j=⟨ri·rj⟩(⟨ri·ri⟩⟨rj·rj⟩)1/2,(6)where ri and rj are the displacement vectors for the i-th and j-th residues in a given mode, respectively, a ⋅ b is the dot product of two vectors a and b, and ⟨a⟩ is the average value of a within the first k lowest frequency modes. Fig 5 shows the cooperativity of residue motions within each subunit and across the whole protein complex. The cooperativity plot is generated from the first 15 dominant (i.e., lowest frequency) modes given by the coarse-grained ssNMA.


Bridging between NMA and Elastic Network Models: Preserving All-Atom Accuracy in Coarse-Grained Models.

Na H, Jernigan RL, Song G - PLoS Comput. Biol. (2015)

Cooperativity of residue motions using the first 15 lowest frequency modes of the coarse-grained ssNMA model.(A) The cooperativity within a single set of subunits: chain A from the cis ring, chain H from the trans ring, and chain O from GroES. (B) The cooperativity among all residue pairs in the GroEL/GroES complex.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4608564&req=5

pcbi.1004542.g005: Cooperativity of residue motions using the first 15 lowest frequency modes of the coarse-grained ssNMA model.(A) The cooperativity within a single set of subunits: chain A from the cis ring, chain H from the trans ring, and chain O from GroES. (B) The cooperativity among all residue pairs in the GroEL/GroES complex.
Mentions: The motion correlation (or cooperativity) Ci,j between the i-th and j-th residues can be expressed as follows:Ci,j=⟨ri·rj⟩(⟨ri·ri⟩⟨rj·rj⟩)1/2,(6)where ri and rj are the displacement vectors for the i-th and j-th residues in a given mode, respectively, a ⋅ b is the dot product of two vectors a and b, and ⟨a⟩ is the average value of a within the first k lowest frequency modes. Fig 5 shows the cooperativity of residue motions within each subunit and across the whole protein complex. The cooperativity plot is generated from the first 15 dominant (i.e., lowest frequency) modes given by the coarse-grained ssNMA.

Bottom Line: For this reason, coarse-grained models have been used successfully.The result is highly significant since it can provide descriptions of normal mode motions at an all-atom level of accuracy even for the largest biomolecular complexes.The application of our method to GroEL/GroES offers new insights into the mechanism of this biologically important chaperonin, such as that the conformational transitions of this protein complex in its functional cycle are even more strongly connected to the first few lowest frequency modes than with other coarse-grained models.

View Article: PubMed Central - PubMed

Affiliation: Department of Computer Science, Iowa State University, Ames, Iowa, United States of America.

ABSTRACT
Dynamics can provide deep insights into the functional mechanisms of proteins and protein complexes. For large protein complexes such as GroEL/GroES with more than 8,000 residues, obtaining a fine-grained all-atom description of its normal mode motions can be computationally prohibitive and is often unnecessary. For this reason, coarse-grained models have been used successfully. However, most existing coarse-grained models use extremely simple potentials to represent the interactions within the coarse-grained structures and as a result, the dynamics obtained for the coarse-grained structures may not always be fully realistic. There is a gap between the quality of the dynamics of the coarse-grained structures given by all-atom models and that by coarse-grained models. In this work, we resolve an important question in protein dynamics computations--how can we efficiently construct coarse-grained models whose description of the dynamics of the coarse-grained structures remains as accurate as that given by all-atom models? Our method takes advantage of the sparseness of the Hessian matrix and achieves a high efficiency with a novel iterative matrix projection approach. The result is highly significant since it can provide descriptions of normal mode motions at an all-atom level of accuracy even for the largest biomolecular complexes. The application of our method to GroEL/GroES offers new insights into the mechanism of this biologically important chaperonin, such as that the conformational transitions of this protein complex in its functional cycle are even more strongly connected to the first few lowest frequency modes than with other coarse-grained models.

No MeSH data available.