To extract biologically-significant information from protein simulation data demands powerful approaches to cluster analysis coupled with statistical-based data-reduction methodologies to visualize the results. Rather than delving into mathematical details, I will take a graphical approach to describe our contributions in this area: automated histogram filtering cluster analysis and squared-loading plots. The following practical applications will be discussed:

Concerted motions in proteins related to their biological function are often referred to as “collective coordinates”. We analyzed molecular dynamics snapshots of an all-atom model of the response regulator protein Spo0F of Bacillus subtilis. Dominant collective coordinates were found to be associated with contiguous stretches of amino acid residues implicated in the biological functioning of Spo0F.

Global measures of structural diversity within a distribution of biopolymers, such as the radius of gyration and percent native contacts, have proven useful in the analysis of simulation data from protein folding. Performing replica exchange Monte Carlo simulations and weighted histogram analysis, we investigated the temperature dependence of Boltzmann-distributed conformations of an off-lattice, all-b protein model. Squared-loading plots provided a local structure-based view of protein folding, capturing structural variability of the model protein at different temperatures. Structural elements having the largest local structural diversity within the sampled distributions were clearly revealed in these plots. They are responsible for peaks and shoulders observed in the specific heat versus temperature curve.

The cyclic AMP receptor protein (CRP) acts as a transcription factor and regulates gene expression related to sugar metabolism. When cyclic AMP (cAMP) binds to CRP, conformation changes and binding to specific DNA sequences occur. Crystal structures of CRP-cAMP-DNA complexes reveal a curved DNA conformation. The structural conformation and curvature of DNA provides insight into the mechanism of transcription and the genomic regulatory process. Automated histogram filtering cluster analysis of a one ns molecular dynamics trajectory of the CRP-cAMP-DNA complex is used independently to determine interactions of CRP-cAMP with each DNA base pair.

□　世話人：田中成典 (発達科学部 自然環境論講座)
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