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for holo as well as apo forms, but low for distorted conformations which are entropically
unfavorable or which involve interpenetrating domains.
A fitness function containing the above terms can be sketched out on the basis of physical
arguments and adjusted empirically. Binding energy is clearly related to the correctness
of the protein structure. Stability is high for both apo and holo, and further is only
estimated here. The quantity was found to be somewhat noisy and so a weighting factor
was used to reduce its influence. Holm and Sander[35] model the interaction between
domains as quadratic, arguing that under the Lennard-Jones model of van der Waals
interactions this approximation holds over a substantial range. Accordingly, the gyration
radius appears squared. Domain distortion can be thought of in the normal mode basis as
a displacement against an elastic potential, but here is reported in units of RMSD, and so
the weighting factor is entirely empirical. The weighting factors applied to all of the
terms except binding energy are determined below. Minimizing the resulting fitness
function can lead to correct generation and identification of the holo structure for domain
hinge bending proteins given only the apo structure, as we will show. We fitted weights
to each of the terms in the fitness function such as to maximize the method’s performance
for Glutamine Binding Protein, as we will explain in the section of that name.
Method
As mentioned, the method requires the identification of the hinge, rotations based on that
hinge, followed by optional equilibrations and docking runs. The direction of the
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