Limits...
Comparison of molecular dynamics and superfamily spaces of protein domain deformation.

Velázquez-Muriel JA, Rueda M, Cuesta I, Pascual-Montano A, Orozco M, Carazo JM - BMC Struct. Biol. (2009)

Bottom Line: Theoretically, we obtained two conclusions.First, that function restricts the access to some flexibility patterns to evolution, as we observe that when a superfamily member changes to become another, the path does not completely overlap with the physical deformability.Methodologically, the conclusion is that both spaces studied are complementary, and have different size and complexity.

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Affiliation: Centro Nacional de Biotecnología-CSIC, Campus Universidad Autónoma, 28049 Madrid, Spain. javi.velazquez@gmail.com

ABSTRACT

Background: It is well known the strong relationship between protein structure and flexibility, on one hand, and biological protein function, on the other hand. Technically, protein flexibility exploration is an essential task in many applications, such as protein structure prediction and modeling. In this contribution we have compared two different approaches to explore the flexibility space of protein domains: i) molecular dynamics (MD-space), and ii) the study of the structural changes within superfamily (SF-space).

Results: Our analysis indicates that the MD-space and the SF-space display a significant overlap, but are still different enough to be considered as complementary. The SF-space space is wider but less complex than the MD-space, irrespective of the number of members in the superfamily. Also, the SF-space does not sample all possibilities offered by the MD-space, but often introduces very large changes along just a few deformation modes, whose number tend to a plateau as the number of related folds in the superfamily increases.

Conclusion: Theoretically, we obtained two conclusions. First, that function restricts the access to some flexibility patterns to evolution, as we observe that when a superfamily member changes to become another, the path does not completely overlap with the physical deformability. Second, that conformational changes from variation in a superfamily are larger and much simpler than those allowed by physical deformability. Methodologically, the conclusion is that both spaces studied are complementary, and have different size and complexity. We expect this fact to have application in fields as 3D-EM/X-ray hybrid models or ab initio protein folding.

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Example of coverage of the essential MD-space achieved by SF-space. The limits of the essential MD-space were determined by the smallest and largest projection values achieved during 10 ns trajectories (10000 structures, red). The essential MD-space was divided in 9 equivalent portions and coverage was evaluated as the number of portions of the essential MD-space visited by at least one superfamily structure (blue).
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Figure 10: Example of coverage of the essential MD-space achieved by SF-space. The limits of the essential MD-space were determined by the smallest and largest projection values achieved during 10 ns trajectories (10000 structures, red). The essential MD-space was divided in 9 equivalent portions and coverage was evaluated as the number of portions of the essential MD-space visited by at least one superfamily structure (blue).

Mentions: 4) The coverage of MD-space achieved by the SF-space was measured by analyzing the distribution of the projections of the superfamily members on the essential subspace defined by the two first singular vectors of the MD-space (essential MD-space). The essential MD-space was divided into 9 equivalent portions were the maximum X and Y values were determined by the smallest and largest projection values achieved during the 10 ns trajectories. The coverage was evaluated as the number of portions of the MD-essential space that were visited by at least one superfamily member (example in Figure 10). Similar results were obtained changing the number of portions. Note that a low coverage can obey to the intrinsic differences between MD and superfamily-derived samplings, but also to the limited number of superfamily members available. In order to distinguish between both sources of deviation we also computed the coverage for the partial MD-space.


Comparison of molecular dynamics and superfamily spaces of protein domain deformation.

Velázquez-Muriel JA, Rueda M, Cuesta I, Pascual-Montano A, Orozco M, Carazo JM - BMC Struct. Biol. (2009)

Example of coverage of the essential MD-space achieved by SF-space. The limits of the essential MD-space were determined by the smallest and largest projection values achieved during 10 ns trajectories (10000 structures, red). The essential MD-space was divided in 9 equivalent portions and coverage was evaluated as the number of portions of the essential MD-space visited by at least one superfamily structure (blue).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2666742&req=5

Figure 10: Example of coverage of the essential MD-space achieved by SF-space. The limits of the essential MD-space were determined by the smallest and largest projection values achieved during 10 ns trajectories (10000 structures, red). The essential MD-space was divided in 9 equivalent portions and coverage was evaluated as the number of portions of the essential MD-space visited by at least one superfamily structure (blue).
Mentions: 4) The coverage of MD-space achieved by the SF-space was measured by analyzing the distribution of the projections of the superfamily members on the essential subspace defined by the two first singular vectors of the MD-space (essential MD-space). The essential MD-space was divided into 9 equivalent portions were the maximum X and Y values were determined by the smallest and largest projection values achieved during the 10 ns trajectories. The coverage was evaluated as the number of portions of the MD-essential space that were visited by at least one superfamily member (example in Figure 10). Similar results were obtained changing the number of portions. Note that a low coverage can obey to the intrinsic differences between MD and superfamily-derived samplings, but also to the limited number of superfamily members available. In order to distinguish between both sources of deviation we also computed the coverage for the partial MD-space.

Bottom Line: Theoretically, we obtained two conclusions.First, that function restricts the access to some flexibility patterns to evolution, as we observe that when a superfamily member changes to become another, the path does not completely overlap with the physical deformability.Methodologically, the conclusion is that both spaces studied are complementary, and have different size and complexity.

View Article: PubMed Central - HTML - PubMed

Affiliation: Centro Nacional de Biotecnología-CSIC, Campus Universidad Autónoma, 28049 Madrid, Spain. javi.velazquez@gmail.com

ABSTRACT

Background: It is well known the strong relationship between protein structure and flexibility, on one hand, and biological protein function, on the other hand. Technically, protein flexibility exploration is an essential task in many applications, such as protein structure prediction and modeling. In this contribution we have compared two different approaches to explore the flexibility space of protein domains: i) molecular dynamics (MD-space), and ii) the study of the structural changes within superfamily (SF-space).

Results: Our analysis indicates that the MD-space and the SF-space display a significant overlap, but are still different enough to be considered as complementary. The SF-space space is wider but less complex than the MD-space, irrespective of the number of members in the superfamily. Also, the SF-space does not sample all possibilities offered by the MD-space, but often introduces very large changes along just a few deformation modes, whose number tend to a plateau as the number of related folds in the superfamily increases.

Conclusion: Theoretically, we obtained two conclusions. First, that function restricts the access to some flexibility patterns to evolution, as we observe that when a superfamily member changes to become another, the path does not completely overlap with the physical deformability. Second, that conformational changes from variation in a superfamily are larger and much simpler than those allowed by physical deformability. Methodologically, the conclusion is that both spaces studied are complementary, and have different size and complexity. We expect this fact to have application in fields as 3D-EM/X-ray hybrid models or ab initio protein folding.

Show MeSH