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1In Plewczynski et al.'s study, only the native ligand conformation is provided.
Further stabilization of this activation segment conformation is provided by a hydrogen bond between Thr at the tip of the P+1 loop and the HRD motif Asp and a conserved salt bridge between Glu from the αEF and the αH/αI Arg.
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An excellent example of HDX MS analysis of protein conformation was provided by Lee et al. wherein they describe the conformational changes of the LOV (light oxygen voltage) domain protein VIVID (VVD) in the absence and presence of the light.
We found that the presence of the native ligand conformation greatly influenced PharmDock's performance in pose prediction: when native ligand conformation was provided together with the low energy conformations in docking, PharmDock was able to reproduce the native binding pose within an RMSDtop ≤ 2 Å for 56% of the protein-ligand complexes.
A notable example of chelation control of conformation was provided by trisaccharide 29 (Scheme 8 ).
b The most probable distances in each type of conformation are provided in Tables S1 and S2 of the Supporting Information.
Additional powerful support for the taxol binding conformation was provided by the synthesis of bridged paclitaxels locked into conformations designed to mimic those of T-taxol.
For instance, to design an XOR gate, four meta-stable partial conformations are provided.
When the native ligand conformations were provided together with the low-energy conformations, PharmDock was able to predict binding poses with RMSDtop ≤ 1 Å for 45% of the tested protein-ligand complexes.
When the native conformations were provided together with the low-energy conformations in docking, PharmDock was able to predict a correct binding pose (RMSD ≤ 2 Å) for 56% of the complexes with an average RMSDtop of 2.9 Å.
Occupancy of individual conformations is listed in Table 2. PDB files with main conformations are provided in Supplementary Material.
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