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Summary: Intramolecular Signaling Pathways Revealed by
Modeling Anisotropic Thermal Diffusion
Nobuyuki Ota and David A. Agard*
Howard Hughes Medical
Institute and Department of
Biochemistry and Biophysics
University of California
San Francisco, CA 94143-2240
USA
A variety of experimental evidence suggests that rapid, long-range
propagation of conformational changes through the core of proteins
plays a vital role in allosteric communication. Here, we describe a non-
equilibrium molecular dynamics simulation method, anisotropic thermal
diffusion (ATD), which allowed us to observe a dominant intramolecular
signaling pathway in PSD-95, a member of the PDZ domain protein family.
The observed pathway is in good accordance with a pathway previously
inferred using a multiple sequence analysis of 276 PDZ domain proteins. In
comparison with conventional solution molecular dynamics methods, the
ATD method provides greatly enhanced signal-to-noise, allowing long-
distance correlations to be observed clearly. The ATD method requires
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