We assumed that MD simulation could produce diverse conformations that could reasonably represent the whole conformational space of domain-peptide complexes.
In the best-conformer-pair approach, a similarity score between a single conformer and a compound (or between two compounds), where each compound has multiple diverse conformations, is represented by the greatest similarity score among all conformer pairs considered per conformer-compound pair (or compound-compound pair).
Diverse conformations within 20 kcal/mol energy range were generated and submitted to the alignment procedure.
The CohB2 structures also displayed diverse conformations in their linker segments.
Prior to the generation of pharmacophore hypotheses, the training set compounds, which were converted to 3D structure, were used to generate diverse conformations.
Instead of (if you will join me in switching visual metaphors) the latticework of a molecule, dots of varying size and composition, connected to some by one bond, others by two, with diverse conformations, chiralities, and no clear center (this metaphor excludes nice symmetrical structures like benzene, obviously) — why don't we attempt something more like the atom itself?
Prior to the generation of pharmacophore hypotheses, the training set compounds (A1, A9, B1, B5, B9, C3, D5, E3, E5, F3, F5, G3, G5, H5, I3, and J5) were converted to 3D structure and were used to generate diverse conformations.
Producing these proteins in other systems has been difficult as diverse conformations occur and the proteins are glycosylated when produced in eukaryotic systems whilst native Pfs25 and Pfs28 from the parasite are not.
While the four reshaped loops exhibit diverse conformations (with shifts in Cα positions up to 20.4 Å), the β-barrel core of the lipocalin remains strongly conserved, thus confirming the extraordinary robustness of this scaffold.
