This Article Full Text Full Text (PDF) All Versions of this Article: biophysj.105.065664v1 89/5/2939    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Van Wynsberghe, A. W. Articles by Cui, Q. Search for Related Content PubMed PubMed Citation Articles by Van Wynsberghe, A. W. Articles by Cui, Q.

Comparison of Mode Analyses at Different Resolutions Applied to Nucleic Acid Systems

Adam W. Van Wynsberghe ^* and Qiang Cui ^* 

^* Graduate Program in Biophysics and Department of Chemistry and Theoretical Chemistry Institute, University of Wisconsin, Madison, Wisconsin

Correspondence: Address reprint requests to Q. Cui, Tel.: 608-262-9801; E-mail: cui{at}chem.wisc.edu.

More than two decades of different types of mode analyses has shown that these techniques can be useful in describing large-scale motions in protein systems. A number of mode analyses are available and include quasiharmonics, classical normal mode, block normal mode, and the elastic network model. Each of these methods has been validated for protein systems and this variety allows researchers to choose the technique that gives the best compromise between computational cost and the level of detail in the calculation. These same techniques have not been systematically tested for nucleic acid systems, however. Given the differences in interactions and structural features between nucleic acid and protein systems, the validity of these techniques in the protein regime cannot be directly translated into validity in the nucleic acid realm. In this work, we investigate the usefulness of the above mode analyses as applied to two RNA systems, i.e., the hammerhead ribozyme and a guanine riboswitch. We show that classical normal-mode analysis can match the magnitude and direction of residue fluctuations from the more detailed, anharmonic technique, quasiharmonic analysis of a molecular dynamics trajectory. The block normal-mode approximation is shown to hold in the nucleic acid systems studied. Only the mode analysis at the lowest level of detail, the elastic network model, produced mixed results in our calculations. We present data that suggest that the elastic network model, with the popular parameterization, is not best suited for systems that do not have a close packed structure; this observation also hints at why the elastic network model has been found to be valid for many globular protein systems. The different behaviors of block normal-mode analysis and the elastic network model, which invoke similar degrees of coarse-graining to the dynamics but use different potentials, suggest the importance of applying a heterogeneous potential function in a robust analysis of the dynamics of biomolecules, especially those that are not closely packed. In addition to these comparisons, we briefly discuss insights into the conformational space available to the hammerhead ribozyme.

This article has been cited by other articles:

				S. Fulle and H. Gohlke Analyzing the Flexibility of RNA Structures by Constraint Counting Biophys. J., June 1, 2008; 94(11): 4202 - 4219. [Abstract] [Full Text] [PDF]

				L. Zhou and S. A. Siegelbaum Effects of Surface Water on Protein Dynamics Studied by a Novel Coarse-Grained Normal Mode Approach Biophys. J., May 1, 2008; 94(9): 3461 - 3474. [Abstract] [Full Text] [PDF]

				K. Reblova, E. Fadrna, J. Sarzynska, T. Kulinski, P. Kulhanek, E. Ennifar, J. Koca, and J. Sponer Conformations of Flanking Bases in HIV-1 RNA DIS Kissing Complexes Studied by Molecular Dynamics Biophys. J., December 1, 2007; 93(11): 3932 - 3949. [Abstract] [Full Text] [PDF]

				C. Musselman, H. M. Al-Hashimi, and I. Andricioaei iRED Analysis of TAR RNA Reveals Motional Coupling, Long-Range Correlations, and a Dynamical Hinge Biophys. J., July 15, 2007; 93(2): 411 - 422. [Abstract] [Full Text] [PDF]

				D. A. Kondrashov, Q. Cui, and G. N. Phillips Jr. Optimization and Evaluation of a Coarse-Grained Model of Protein Motion Using X-Ray Crystal Data Biophys. J., October 15, 2006; 91(8): 2760 - 2767. [Abstract] [Full Text] [PDF]

				L.-W. Yang, A. J. Rader, X. Liu, C. J. Jursa, S. C. Chen, H. A. Karimi, and I. Bahar oGNM: online computation of structural dynamics using the Gaussian Network Model. Nucleic Acids Res., July 1, 2006; 34(Web Server issue): W24 - W31. [Abstract] [Full Text] [PDF]