Sensitivity tests suggest that the problem is sufficiently serious to consider an alternative approach by either zonal modelling or explicit modelling of inactive turbulence effects.
Imatinib, dasatinib, sunitinib, CEP-701, and PKC-412, ATP-competitive small molecule inhibitors of type III receptor tyrosine kinases c-KIT and/or FLT3, were evaluated for binding to the closely related receptor, FMS, by docking into models of inactive and active conformations of the FMS kinase domain.
A "homology model" of the inactive conformation of Plk1 was constructed, as the crystal structure in its inactive conformation is unknown.
In addition to the blocking segments, a cluster of hydrophobic amino acid residues centred about Val appears to stabilize the inactive conformer, and a substitution of a glutamate residue for Val in the model of the inactive procaspase-3 suggests a mechanism for activation resulting from the mutation.
The design of analogues was guided by the docking of potential compounds into a model of the inactive form of GPR55.
The model of the inactive conformation of the TSHR TMD predicts an aromatic interaction between Phe5945.51 and Phe6346.54 at 2.9 Å (Supplementary Table 6, Fig. 3d).
From these studies, a model of the inactive and active states of PhoB has been proposed that involves the formation of two distinct dimers.
In the model of the inactive conformation of the LHR TMD wild type, the beta carbon atom of Ala5936.59 forms a hydrophobic interaction at 3.4 Å with the delta 1 carbon atom of Ile5285.40 (Supplementary Table 5).
A proposed direct interaction between Asp6336.44 and Asn6747.49, based on mutations experiments [38], is not observed in the structure of the model of the inactive TSHR TMD; however, a water-mediated hydrogen bond is possible (distance of 4.6 Å).
