Decoding
the Mobility and Time Scales of Protein Loops
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Abstract
The
flexible nature of protein loops and the time scales of their
dynamics are critical for many biologically important events at the
molecular level, such as protein interaction and recognition processes.
In order to obtain a predictive understanding of the dynamic properties
of loops, 500 ns molecular dynamics (MD) computer simulations of 38
different proteins were performed and validated using NMR chemical
shifts. A total of 169 loops were analyzed and classified into three
types, namely fast loops with correlation times <10 ns, slow loops
with correlation times between 10 and 500 ns, and loops that are static
over the course of the whole trajectory. Chemical and biophysical
loop descriptors, such as amino-acid sequence, average 3D structure,
charge distribution, hydrophobicity, and local contacts were used
to develop and parametrize the ToeLoop algorithm for the prediction
of the flexibility and motional time scale of every protein loop,
which is also implemented as a public Web server (http://spin.ccic.ohio-state.edu/index.php/loop). The results demonstrate that loop dynamics with their time scales
can be predicted rapidly with reasonable accuracy, which will allow
the screening of average protein structures to help better understand
the various roles loops can play in the context of protein–protein
interactions and binding