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Domains can move relative to each other only if the motion is permitted energetically.
Thus if two domains have many interdomain interactions they are unlikely to separate.
Similarly, if a motion results in the exposure of large hydrophobic areas on the protein,
then the energetic and entropic cost of solvation will make that motion less likely to
occur.
For these reasons, we argue that if two or more domains are joined by a hinge, and if a
peptide bond is broken on the protein, the energetic cost of separating and solvating the
two resulting fragments will be lowest if that break is in a hinge. Conversely, if the break
is inside a rigid domain, the energetic cost will be high. We will show how this idea
leads to a hinge prediction method.
Single-cut hinge predictor (TINKER version)
The idea of evaluating the cost of separating two fragments can be implemented using the
minimization and single point energy evaluation features available in almost any
molecular mechanics engine. This energy of separation is equivalent, up to an additive
constant, to the difference in single-point energies between the two fragments generated
by introducing a single cut on the protein chain on the one hand, and the original,
undivided chain on the other hand. This energy evaluation can be carried out using a
standard force field for every choice of cut location, and the resulting energy vs. cut
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