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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.


Related in: MedlinePlus

Preservation of secondary structures in mode motions.The solid red (or black) line represents the average structure deviations of all secondary structures of the GroEL/GroES complex when it moves along a normal mode of ssNMA (or ANM). The dashed lines are the least-square fits to the solid lines.
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pcbi.1004542.g007: Preservation of secondary structures in mode motions.The solid red (or black) line represents the average structure deviations of all secondary structures of the GroEL/GroES complex when it moves along a normal mode of ssNMA (or ANM). The dashed lines are the least-square fits to the solid lines.

Mentions: Fig 7 shows how well the quality of the secondary structures are preserved as the protein complex moves in the directions of the modes of ssNMA or ANM. In this study, for each mode, the protein structure is deformed along the mode direction until its RMSD changes 1 Å from the initial structure. The RMSDs of individual secondary structures (alpha-helices or beta-sheets) are determined independently, and the average RMSDs of these secondary structures are then computed. This procedure is repeated for the first 100 lowest frequency modes of both coarse-grained ssNMA and ANM. In the figure, the solid red (black) line represents the secondary structure deviations by the coarse-grained ssNMA (or ANM), and the dashed lines are the least-square fits to the solid lines. The plot shows that secondary structures are preserved about twice as well with ssNMA as with ANM.


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)

Preservation of secondary structures in mode motions.The solid red (or black) line represents the average structure deviations of all secondary structures of the GroEL/GroES complex when it moves along a normal mode of ssNMA (or ANM). The dashed lines are the least-square fits to the solid lines.
© Copyright Policy
Related In: Results  -  Collection

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

pcbi.1004542.g007: Preservation of secondary structures in mode motions.The solid red (or black) line represents the average structure deviations of all secondary structures of the GroEL/GroES complex when it moves along a normal mode of ssNMA (or ANM). The dashed lines are the least-square fits to the solid lines.
Mentions: Fig 7 shows how well the quality of the secondary structures are preserved as the protein complex moves in the directions of the modes of ssNMA or ANM. In this study, for each mode, the protein structure is deformed along the mode direction until its RMSD changes 1 Å from the initial structure. The RMSDs of individual secondary structures (alpha-helices or beta-sheets) are determined independently, and the average RMSDs of these secondary structures are then computed. This procedure is repeated for the first 100 lowest frequency modes of both coarse-grained ssNMA and ANM. In the figure, the solid red (black) line represents the secondary structure deviations by the coarse-grained ssNMA (or ANM), and the dashed lines are the least-square fits to the solid lines. The plot shows that secondary structures are preserved about twice as well with ssNMA as with ANM.

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.


Related in: MedlinePlus