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strikingly similar both to the holo (inset 5.7.d) and to the starting structure (inset 5.7.b).
This striking success at correctly predicting that the open form is the holo for this ligand
indicates that we have included some of the physically important phenomena in our
fitness function.
Discussion
Prediction of protein conformational change
For Biotin carboxylase and Glutamine binding protein, large scale motions of the M
domain are required for binding, and computational expense makes predicting them by
Molecular Dynamics impractical for many applications. We showed that in the ligand
binding application our method generates and correctly identifies the bound conformation
of GlnBP, with an sRMSD dropping from 15.7Å for the starting or apo structure down to
3.6Å for the predicted structure. For biotin carboxylase, sequence differences between
the holo and starting structures limited the structural alignment somewhat, but the closed
conformation was nonetheless clearly predicted, with sRMSD dropping from 14.8Å to
7.0Å. For MurA, minimal domain motion was required for binding, and this was also
predicted correctly, with sRMSD remaining constant at around 5Å. (Table 1).
Potential applications and future work
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