2000 putative NBD1–NBD2 binding configurations were retained
in the ZDOCK final results. These 2000 NBD1–NBD2 binding
configurations from ZDOCK were further refined and rescored
using a more accurate scoring function, ITScore-PP, recently
developed in our group[28]. The top NBD1–NBD2 binding mode
that has the lowest ITScore-PP score was chosen. This predicted
structure was then optimized via AMBER force field minimization.
The optimized NBD1–NBD2 structure was used as the protein
target for docking ATP and genistein.
It should be noted that the C-terminal extension of NBD1 into
the R domain (i.e., the last 31 residues at the C-terminus) was not
included in ourmodeling study for two reasons. First, this segment
was found to exhibit prominent flexibility in crystallographic
studies [9,11]. Second, our functional studies with DR-CFTR
suggest that a deletion of the R domain has little effect on CFTR
gating[29–32]. It should also be noted that residues 412–428 were
missing in the crystal structure (1XMI) and therefore were not
included in the present modeling study.
2000 putative NBD1–NBD2 binding configurations were retained
in the ZDOCK final results. These 2000 NBD1–NBD2 binding
configurations from ZDOCK were further refined and rescored
using a more accurate scoring function, ITScore-PP, recently
developed in our group[28]. The top NBD1–NBD2 binding mode
that has the lowest ITScore-PP score was chosen. This predicted
structure was then optimized via AMBER force field minimization.
The optimized NBD1–NBD2 structure was used as the protein
target for docking ATP and genistein.
It should be noted that the C-terminal extension of NBD1 into
the R domain (i.e., the last 31 residues at the C-terminus) was not
included in ourmodeling study for two reasons. First, this segment
was found to exhibit prominent flexibility in crystallographic
studies [9,11]. Second, our functional studies with DR-CFTR
suggest that a deletion of the R domain has little effect on CFTR
gating[29–32]. It should also be noted that residues 412–428 were
missing in the crystal structure (1XMI) and therefore were not
included in the present modeling study.
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