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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

Comparisons of the experimental B-factors with the mean-square fluctuations (MSFs) computed with the new coarse-grained ssNMA and with ANM, for (A) all residues and (B) only the first subunit in each ring.The middle gray region is the trans-ring of GroEL, and the left and right white regions are the cis-ring of GroEL and the GroES cap, respectively.
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pcbi.1004542.g004: Comparisons of the experimental B-factors with the mean-square fluctuations (MSFs) computed with the new coarse-grained ssNMA and with ANM, for (A) all residues and (B) only the first subunit in each ring.The middle gray region is the trans-ring of GroEL, and the left and right white regions are the cis-ring of GroEL and the GroES cap, respectively.

Mentions: Fig 4 shows the mean-square fluctuations (MSFs) determined by CG-ssNMA (in red) and by the coarse-grained Cα-based ANM (in gray), and the experimental B-factors (in black). In (A), all 8015 residues’ MSFs and B-factors are shown for three separate parts: the cis-ring with a white background, the trans-ring with a light gray background, and the GroES cap with a white background. In (B), the first subunits of the three parts (cis and trans rings, and GroES) are re-plotted to show the MSF in more detail. In the figure, the mean-square fluctuations by ssNMA and ANM are computed using all the modes (including all the high-frequency modes) and scaled to minimize the root-mean-square deviation from the experimental B-factors. The correlation between experimental and predicted B-factors is 0.69 for ssNMA, and 0.52 for ANM. Note that there are a few high peaks in ssNMA MSFs.


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)

Comparisons of the experimental B-factors with the mean-square fluctuations (MSFs) computed with the new coarse-grained ssNMA and with ANM, for (A) all residues and (B) only the first subunit in each ring.The middle gray region is the trans-ring of GroEL, and the left and right white regions are the cis-ring of GroEL and the GroES cap, respectively.
© Copyright Policy
Related In: Results  -  Collection

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

pcbi.1004542.g004: Comparisons of the experimental B-factors with the mean-square fluctuations (MSFs) computed with the new coarse-grained ssNMA and with ANM, for (A) all residues and (B) only the first subunit in each ring.The middle gray region is the trans-ring of GroEL, and the left and right white regions are the cis-ring of GroEL and the GroES cap, respectively.
Mentions: Fig 4 shows the mean-square fluctuations (MSFs) determined by CG-ssNMA (in red) and by the coarse-grained Cα-based ANM (in gray), and the experimental B-factors (in black). In (A), all 8015 residues’ MSFs and B-factors are shown for three separate parts: the cis-ring with a white background, the trans-ring with a light gray background, and the GroES cap with a white background. In (B), the first subunits of the three parts (cis and trans rings, and GroES) are re-plotted to show the MSF in more detail. In the figure, the mean-square fluctuations by ssNMA and ANM are computed using all the modes (including all the high-frequency modes) and scaled to minimize the root-mean-square deviation from the experimental B-factors. The correlation between experimental and predicted B-factors is 0.69 for ssNMA, and 0.52 for ANM. Note that there are a few high peaks in ssNMA MSFs.

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