Cooperative Conformational Changes in Globular Proteins

Pohl, Fritz M.

doi:10.1002/anie.197208941

Cited by 24 publications

(1 citation statement)

References 85 publications

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“…has been a major challenge in biophysics (1,2). With advances in macromolecular crystallography, structural information has been obtained on very large complexes such as ribosome particles (3), chaperone complexes (4), virus particles (5), and RNA polymerases (6) as well as on thousands of individual proteins.…”

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A force field for virtual atom molecular mechanics of proteins

Korkut¹,

Hendrickson

2009

Proc. Natl. Acad. Sci. U.S.A.

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Activities of many biological macromolecules involve large conformational transitions for which crystallography can specify atomic details of alternative end states, but the course of transitions is often beyond the reach of computations based on full-atomic potential functions. We have developed a coarse-grained force field for molecular mechanics calculations based on the virtual interactions of C␣ atoms in protein molecules. This force field is parameterized based on the statistical distribution of the energy terms extracted from crystallographic data, and it is formulated to capture features dependent on secondary structure and on residue-specific contact information. The resulting force field is applied to energy minimization and normal mode analysis of several proteins. We find robust convergence in minimizations to low energies and energy gradients with low degrees of structural distortion, and atomic fluctuations calculated from the normal mode analyses correlate well with the experimental B-factors obtained from high-resolution crystal structures. These findings suggest that the virtual atom force field is a suitable tool for various molecular mechanics applications on large macromolecular systems undergoing large conformational changes.energy minimization ͉ normal modes ͉ transition pathways A ccurate understanding of the dynamic properties of proteins has been a major challenge in biophysics (1, 2). With advances in macromolecular crystallography, structural information has been obtained on very large complexes such as ribosome particles (3), chaperone complexes (4), virus particles (5), and RNA polymerases (6) as well as on thousands of individual proteins. In addition, snapshots of protein structures in different states of activity demonstrate the existence of very large conformational changes (7,8). Computational analysis of the dynamics of such systems is extremely difficult, if not impossible, when using full-atomic computational approaches, due not only to computational limitations but also to the complexity of the resulting information. Thus, coarse-grained approaches have gained importance for addressing large systems and large conformational changes (9-11).Coarse graining reduces computational complexity by greatly decreasing degrees of freedom of a molecular system with appropriate assumptions to achieve simplification without compromise of essential features (12). For reducing complexity in proteins, C␣-only models have been the most popular, but other coarse-graining approaches have also been taken, such as the inclusion of side-chain centroids (SCs) (13). An important aspect of coarse-grained analysis is the use of an appropriate pseudoforce field to model the forces and constraints exerted on the molecular system.The use of simple harmonic potentials to model the C␣-to-C␣ interactions in proteins as flexible springs has been most popular (14). Such simple harmonic potentials are very effective in defining the near-native-state fluctuations of proteins calculated by elastic network models...

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confidence: 99%

A force field for virtual atom molecular mechanics of proteins

Korkut¹,

Hendrickson

2009

Proc. Natl. Acad. Sci. U.S.A.

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Cooperative Conformational Kinetics of Synthetic and Biological Chain Molecules

Cerf

1975

Advances in Chemical Physics

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Molekulare Hysterese und ihre kybernetische Bedeutung

Neumann

1973

Angewandte Chemie

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Die allgemeinen Grundlagen für die thermodynamische Analyse von Hystereseerscheinungen in Lösungen und Suspensionen polyelektrolytischer Systeme werden anhand von Beispielen molekularer Hysterese in Biopolymeren und Membranen dargelegt. Die fundamentale kybernetische Bedeutung metastabiler Zustände und molekularer Hysterese für die physikalische Interpretation von Lebenserscheinungen wie Gedächtnisaufzeichnung und biologische Rhythmen wird diskutiert.

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Cooperative Conformational Changes in Globular Proteins

Cited by 24 publications

References 85 publications

A force field for virtual atom molecular mechanics of proteins

A force field for virtual atom molecular mechanics of proteins

Cooperative Conformational Kinetics of Synthetic and Biological Chain Molecules

Molekulare Hysterese und ihre kybernetische Bedeutung

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