@entity10783 oligopeptidase (POP) is considered as an important pharmaceutical target for the treatment of @entity66 . Despite enormous studies on various aspects of POPs structure and function still some of the questions are intriguing like conformational dynamics of the protein and interplay between ligand entry/egress. Here, we have used molecular modeling and docking based approaches to unravel questions like differences in ligand binding affinities in three POP species (porcine, @entity1 and A. thaliana). Despite high sequence and structural similarity, they possess different affinities for the ligands. Interestingly, @entity1 POP was found to be more specific, selective and incapable of binding to a few planar ligands which showed extrapolation of porcine POP in @entity1 context is more complicated. Possible routes for substrate entry and product egress were also investigated by detailed analyses of @entity74 ( @entity74 ) simulations for the three proteins. Trajectory analysis of bound and unbound forms of three species showed differences in conformational dynamics, especially variations in b-propeller pore size, which was found to be hidden by five @entity376 residues present on blades one and seven. During simulation, b-propeller pore size was increased by    2    in porcine ligand-bound form which might act as a passage for smaller product movement as free energy barrier was reduced, while there were no significant changes in @entity1 and A. thaliana POPs. We also suggest that these differences in pore size could lead to fundamental differences in mode of product egress among three species. This analysis also showed some functionally important residues which can be used further for in vitro mutagenesis and inhibitor design. This study can help us in better understanding of the etiology of POPs in several @entity179 .

Structural analysis of XXXX oligopeptidases using molecular docking and dynamics: insights into conformational changes and ligand binding.

@entity1 :: ('9606', 'Species') :: ['human'] @entity66 :: ('MESH:D004194', 'Disease') :: ['numerous diseases'] @entity376 :: ('CHEBI:25094', 'Chemical') :: ['lysine'] @entity74 :: ('MESH:D030342', 'Disease') :: ['molecular dynamics', 'MD'] @entity179 :: ('MESH:D019636', 'Disease') :: ['neurodegenerative diseases'] @entity10783 :: ('CHEBI:26274', 'Chemical') :: ['Prolyl']
@entity10783 :: (CHEBI:26274,Chemical) :: ['prolyl']
