Abstract：
:A MD simulation protocol was developed to model halogen bonding in protein-ligand complexes by inclusion of a charged extra point to represent the anisotropic distribution of charge on the halogen atom. This protocol was then used to simulate the interactions of cathepsin L with a series of halogenated and non-halogenated inhibitors. Our results show that chloro, bromo and iodo derivatives have progressively narrower distributions of calculated geometries, which reflects the order of affinity I > Br > Cl, in agreement with the IC50 values. Graphs for the Cl, Br and I analogs show stable interactions between the halogen atom and the Gly61 carbonyl oxygen of the enzyme. The halogen-oxygen distance is close to or less than the sum of the van der Waals radii; the C-X···O angle is about 170°; and the X···O=C angle approaches 120°, as expected for halogen bond formation. In the case of the iodo-substituted analogs, these effects are enhanced by introduction of a fluorine atom on the inhibitors' halogen-bonding phenyl ring, indicating that the electron withdrawing group enlarges the σ-hole, resulting in improved halogen bonding properties.
journal_name
J Comput Aided Mol Desjournal_title
Journal of computer-aided molecular designauthors
Celis-Barros C,Saavedra-Rivas L,Salgado JC,Cassels BK,Zapata-Torres Gdoi
10.1007/s10822-014-9802-7subject
Has Abstractpub_date
2015-01-01 00:00:00pages
37-46issue
1eissn
0920-654Xissn
1573-4951journal_volume
29pub_type
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journal_title：Journal of computer-aided molecular design
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journal_title：Journal of computer-aided molecular design
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journal_title：Journal of computer-aided molecular design
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