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with respect to the starting structure. The point of this measure is not to precisely
indicate the best predicted holo structure but rather to exclude from consideration
particularly distorted and therefore less probable structures, such as the one seen in inset
5.3.f. As mentioned sRMSD is our figure of merit for scoring our predictions. The
generated structure with lowest sRMSD is shown in inset 5.3.c. The reader can verify
that this structure is qualitatively similar to the experimentally known holo structure,
shown in inset 5.3.d.
The structure with lowest docked energy is shown in inset 5.3.e, and is also qualitatively
similar to the holo. The reader may ask, why not use docked energy as the sole
component of the fitness function? The answer is that if this is done the algorithm will
find structures of even lower docked energy which are not only very different from the
holo, but also have significantly distorted or interpenetrating domains, or extreme and
unnatural angular orientations. Further, the gradient of docked energy is not smooth,
leading to various convergence problems. All of these issues are addressed by the
additional terms as we will continue discussing.
The structure with lowest gyration radius is shown in inset 5.3.f. The holo tends to have
a smaller radius of gyration than the apo structure. We found that gyration radius
decreases smoothly between apo and predicted holo structures, and so including it in the
fitness function provides the smoother gradient countering the noise in the docked energy.
Gyration radius cannot be used alone in the fitness function since it is trivially possible to
minimize this quantity with a compact structure which is unstable, has significantly
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