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ending, which involves a rigid region or domain of the protein moving relative to
another domain about a hinge which connects the two.[3, 9] Such motions typically
involve the slowest degrees of freedom of the system and so are difficult to treat by
existing methods.
Despite the challenges, the prediction of conformational change in proteins attracts wide
theoretical and experimental interest. Flexibility, molecular recognition, induced fit,
protein-protein docking, assembly of complexes, elucidation of enzyme reactions,
reaction kinetics and many other fields will benefit from an improved understanding of
this topic.
Much work has been done in this area. Molecular Dynamics[85] explicitly computes the
dynamical trajectory of molecules modeled as point masses connected by linear and
nonlinear springs and can be used to predict conformational change, but usually only
small- to medium-scale domain motions can be reproduced. One problem that the
technique suffers from is the difficulty of escaping the vicinity of an initial conformation
in a reasonable amount of time. Carlson et al.[86] showed how to include the
fluctuations of proteins in drug docking by first computing the protein trajectory using
Molecular Dynamics. This method can treat fast fluctuations but large scale
conformational changes are out of its reach for the same reasons as above.
Normal modes have also been used by many authors to predict the conformational
changes of proteins. Comparison of the atomic coordinates of homologous pairs of
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