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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.


Descriptions of the first 13 lowest frequency modes of GroEL/GroES, determined by the coarse-grained ssNMA. (A) mode 1, (B) mode 3, (C) modes 2 and 4, (D) modes 5 and 6, (E) modes 7 and 8, (F) modes 9 and 10, (G) modes 11, and (H) modes 12 and 13.
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pcbi.1004542.g006: Descriptions of the first 13 lowest frequency modes of GroEL/GroES, determined by the coarse-grained ssNMA. (A) mode 1, (B) mode 3, (C) modes 2 and 4, (D) modes 5 and 6, (E) modes 7 and 8, (F) modes 9 and 10, (G) modes 11, and (H) modes 12 and 13.

Mentions: Fig 6 characterizes the slow dynamics of GroEL/GroES in individual modes or pairs of modes. The first lowest frequency mode portrays a rotational motion around the cylindrical axis of the complex. This mode matches with the first mode of ANM nearly perfectly, with a high overlap of 0.97. The third mode is about opening the gate of the trans ring to receive substrates into its chamber, by moving its apical domains to conform its structure to resemble that of the cis ring. The second and fourth modes are mainly about a swing motion of the trans ring. This motion also helps to open the chamber gate of the trans ring. In ssNMA, this gate opening motion in the trans ring is clearly captured by these three distinct modes, especially the third mode, whose importance is manifested also in the conformation transitions during the GroEL/GroES functional cycle that will be described in the next section. In ANM, there is not a single mode that closely matches the third mode of ssNMA. The gating opening motion seems to spread into several modes in ANM and be mingled with other motions. The 5th–6th modes are shearing motions of the GroES cap and the apical domains of the cis ring. This motion causes them to shift significantly relative to the equatorial domains. This motion (in the 5th/6th modes) is similar, to some extent, to that in the second and third modes of ANM, which in turn have some resemblance also to the second/fourth modes of ssNMA. The 7th–10th modes display alternating motions of compression and extension of the whole complex. The 11th mode is mainly about stretching/compressing the chamber of the cis-ring. To some extent, this motion (of the 11th mode) changes the structure of the cis ring towards the shape of the trans ring. The 12th–13th modes are mainly about tilting the cis/trans rings and the GroES cap.


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)

Descriptions of the first 13 lowest frequency modes of GroEL/GroES, determined by the coarse-grained ssNMA. (A) mode 1, (B) mode 3, (C) modes 2 and 4, (D) modes 5 and 6, (E) modes 7 and 8, (F) modes 9 and 10, (G) modes 11, and (H) modes 12 and 13.
© Copyright Policy
Related In: Results  -  Collection

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

pcbi.1004542.g006: Descriptions of the first 13 lowest frequency modes of GroEL/GroES, determined by the coarse-grained ssNMA. (A) mode 1, (B) mode 3, (C) modes 2 and 4, (D) modes 5 and 6, (E) modes 7 and 8, (F) modes 9 and 10, (G) modes 11, and (H) modes 12 and 13.
Mentions: Fig 6 characterizes the slow dynamics of GroEL/GroES in individual modes or pairs of modes. The first lowest frequency mode portrays a rotational motion around the cylindrical axis of the complex. This mode matches with the first mode of ANM nearly perfectly, with a high overlap of 0.97. The third mode is about opening the gate of the trans ring to receive substrates into its chamber, by moving its apical domains to conform its structure to resemble that of the cis ring. The second and fourth modes are mainly about a swing motion of the trans ring. This motion also helps to open the chamber gate of the trans ring. In ssNMA, this gate opening motion in the trans ring is clearly captured by these three distinct modes, especially the third mode, whose importance is manifested also in the conformation transitions during the GroEL/GroES functional cycle that will be described in the next section. In ANM, there is not a single mode that closely matches the third mode of ssNMA. The gating opening motion seems to spread into several modes in ANM and be mingled with other motions. The 5th–6th modes are shearing motions of the GroES cap and the apical domains of the cis ring. This motion causes them to shift significantly relative to the equatorial domains. This motion (in the 5th/6th modes) is similar, to some extent, to that in the second and third modes of ANM, which in turn have some resemblance also to the second/fourth modes of ssNMA. The 7th–10th modes display alternating motions of compression and extension of the whole complex. The 11th mode is mainly about stretching/compressing the chamber of the cis-ring. To some extent, this motion (of the 11th mode) changes the structure of the cis ring towards the shape of the trans ring. The 12th–13th modes are mainly about tilting the cis/trans rings and the GroES cap.

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.