Identification of dynamical correlations within the myosin motor domain by the normal mode analysis of an elastic network model.
In order to systematically analyze functionally relevant dynamical correlations within macromolecular complexes, we have developed computational methods based on the normal mode analysis of an elastic network model. First, we define two types of dynamical correlations (fluctuation-based and density-based), which are computed by summing up contributions from all low-frequency normal modes up to a given cutoff. Then we use them to select dynamically important "hinge residues" whose elastic distortion affects the fluctuations of a large number of residues. Second, in order to clarify long-range dynamical correlations, we decompose the dynamical correlations to individual normal modes to identify the most relevant modes. We have applied these methods to the analysis of the motor domain of Dictyostelium myosin and have obtained the following three interesting results that shed light on its mechanism of force generation: first, we find the hinge residues are distributed over several key inter-subdomain joints (including the nucleotide-binding pocket, the relay helix, the SH1 helix, the strut between the upper 50 kDa and the lower 50 kDa subdomains), which is consistent with their hypothesized roles in modulating functionally relevant inter-subdomain conformational changes; second, a single mode 7 (for structure 1VOM) is found to dominate the fluctuation-based correlations between the converter/strut and the nucleotide-binding pocket, revealing a surprising simplicity for their intriguing roles in the force generation mechanism; finally, we find a negative density-based correlation between the strut and the nucleotide-binding pocket, which is consistent with the hypothesized signaling pathway that links the actin-binding site's opening/closing with the nucleotide-binding pocket's closing/opening.
Zheng
Wenjun
W
Laboratory of Computational Biology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. zhengwj@helix.nih.gov
Brooks
Bernard
B
D000818:Animals; D001665:Binding Sites; D004023:Dictyostelium / Q000737:chemistry; D004548:Elasticity; D066298:In Vitro Techniques; D008958:Models, Molecular; D020409:Molecular Motor Proteins / Q000737:chemistry*; D009218:Myosins / Q000737:chemistry*; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000737:chemistry; D013816:Thermodynamics
D020409:Molecular Motor Proteins; D015800:Protozoan Proteins; D009218:Myosins