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Threading As a Tool
For Ab Initio Prediction Of 3D Folds Of Proteins:
Possibility And Limitations
Dmitry S. Rykunov
Institute of Theoretical & Experimental Biophysics
RAS, Pushchino, Moscow reg., 142292 Russia
Aim: Our aim is to
apply threading approach to ab initioprediction of
protein folds. As the target folds for treading, we use the sets
of
folding patterns that are partly observed and partly not observed
in
natural protein. Each set is obtained from some native protein
core
using extrapolations of its secondary structure elements and all
the
reasonable modifications of the core topology, i.e. a variety
chain
pathways through this core. The computations are based on the
self
consistent molecular field theory and on the statistical
mechanics of
chain molecules. The molecular field summarizes the action of
long-range interactions. Statistical mechanics finds the stable
state
and fluctuations of the chain in this field.
Results: The developed computer program and the set of generated
frameworks are used to single out the stable folds of a number of
protein chains. It is shown that extrapolation of secondary
structure
segments improves recognition of cognate proteins, and that
extension
of target fold library by reconnectingof secondary structures of
known
protein folds is useful for recognition of "new",
previously not
observed protein folds. However, in a general case the native
fold is
recognized as one of the most stable, but rarely as the most
stable
chain fold.
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