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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.


Structure of the GroEL/GroES complex in (A) front and (B) top views.For subunits of the GroEL, the equatorial, intermediate, and apical domains of cis and trans rings are colored green, yellow, and blue, respectively. The GroES cap is displayed in red.
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pcbi.1004542.g003: Structure of the GroEL/GroES complex in (A) front and (B) top views.For subunits of the GroEL, the equatorial, intermediate, and apical domains of cis and trans rings are colored green, yellow, and blue, respectively. The GroES cap is displayed in red.

Mentions: The GroEL/GroES complex [55] is a molecular chaperone that assists the unfolding of partially folded or misfolded proteins, by providing them with the chance to refold. GroEL consists of cis and trans rings, each of which has 7 subunits. Each subunit is 547 residues. GroES also has 7 chains and each chain contains 97 residues. The GroEL cis-ring and GroES form a capped chamber that can hold proteins and facilitate protein unfolding partly through their intrinsic collective motions, such as compressing, stretching, twisting, shearing, and relaxing. Fig 3 shows the GroEL/GroES structure (pdbid: 1AON) in top and front views. In Fig 3(A), the three domains of the cis and trans rings are distinguished with different colors: equatorial (green), intermediate (yellow), and apical (blue) domains.


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)

Structure of the GroEL/GroES complex in (A) front and (B) top views.For subunits of the GroEL, the equatorial, intermediate, and apical domains of cis and trans rings are colored green, yellow, and blue, respectively. The GroES cap is displayed in red.
© Copyright Policy
Related In: Results  -  Collection

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

pcbi.1004542.g003: Structure of the GroEL/GroES complex in (A) front and (B) top views.For subunits of the GroEL, the equatorial, intermediate, and apical domains of cis and trans rings are colored green, yellow, and blue, respectively. The GroES cap is displayed in red.
Mentions: The GroEL/GroES complex [55] is a molecular chaperone that assists the unfolding of partially folded or misfolded proteins, by providing them with the chance to refold. GroEL consists of cis and trans rings, each of which has 7 subunits. Each subunit is 547 residues. GroES also has 7 chains and each chain contains 97 residues. The GroEL cis-ring and GroES form a capped chamber that can hold proteins and facilitate protein unfolding partly through their intrinsic collective motions, such as compressing, stretching, twisting, shearing, and relaxing. Fig 3 shows the GroEL/GroES structure (pdbid: 1AON) in top and front views. In Fig 3(A), the three domains of the cis and trans rings are distinguished with different colors: equatorial (green), intermediate (yellow), and apical (blue) domains.

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.