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<p>Allosteric conformational changes are among the slowest and most potentially complex events in structural biology. While many aspects of such motions may resemble macroscopic machines and be described as the motion of hinges (<a href="http://www.biology-online.org/articles/references46.htm#REF1">1</a>), unlike macroscopic machines, the functioning of biological machines may involve catastrophic events such as cracking and subsequent reassembly. These large-scale events would normally be unseen in conventional molecular dynamics studies owing to the limited simulation time used. These events can now be explored by using the present theoretical methods in concert with experimental tests. </p>
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