Validated scoring of halogen bonding in molecular design
نویسندگان
چکیده
As a rather new type of non-covalent interaction, halogen bonding is slowly being integrated into molecular modeling and the drug design process. Aromatic halogenated molecules can theoretically form halogen bonds with any electron donor. Based on quantum chemical calculations, we evaluated the interaction energies between several halobenzenes and the oxygen of N-methylacetamide, representing the carbonyl-function of the protein backbone [1,2]. In a ligand-protein complex very rarely optimal interaction geometries are observed. In order to assess all spatial dependencies of the halogen bond with regards to deviations from optimal geometries, our calculations include variations in distance, bond angles and spherical orientation. On this basis we developed a tool for scaffold decoration applicable to any crystal structure or docking result [3]. For every unsubstituted aromatic atom in a ligand the tool determines whether halogenation leads to a favorable halogen bonding interaction with the binding site. A scoring function, derived from a myriad of QM-calculations on the MP2 TZVPP-level of theory, evaluates the quality of the assumed interaction. To assess the prediction accuracy of our scoring function, we initially chose 50 examples from an exhaustive PDB scan randomly, representing the full range of equally distributed halogen bonding scores. For each file, the geometry was then recreated using iodobenzene representing the ligand system and N-methylacetamide as the backbone structure. Thus, the halogen bonding geometry of the database example was transferred as accurately as possible to our small model system and the interaction was calculated as an MP2 single point. The resulting energy was normalized and plotted against the predicted halogen bonding score. With only a few exceptions, most deviations were
منابع مشابه
AutoDock VinaXB: implementation of XBSF, new empirical halogen bond scoring function, into AutoDock Vina
BACKGROUND Halogen bonding has recently come to play as a target for lead optimization in rational drug design. However, most docking program don't account for halogen bonding in their scoring functions and are not able to utilize this new approach. In this study a new and improved halogen bonding scoring function (XBSF) is presented along with its implementation in the AutoDock Vina molecular ...
متن کاملRepositioning organohalogen drugs: a case study for identification of potent B-Raf V600E inhibitors via docking and bioassay
Drug repositioning has been attracting increasingly attention for its advantages of reducing costs and risks. Statistics showed that around one quarter of the marketed drugs are organohalogens. However, no study has been reported, to the best of our knowledge, to aim at efficiently repositioning organohalogen drugs, which may be attributed to the lack of accurate halogen bonding scoring functio...
متن کاملInterplay Between Lithium Bonding and Halogen Bonding in F3CX•••YLi•••NCCN and F3CX•••NCCN•••LiY Complexes (X = Cl, Br; Y = CN, NC)
MP2 calculations with cc-pVTZ basis set were used to analyze intermolecular interactions in F3CX···YLi···NCCN and F3CX···NCCN···LiY triads (X = Cl, Br; Y = CN, NC) which are connected via halogen and lithium bonds. Those complexes with the role of LiY as halogen acceptor and lithium donor show cooperativity with energy values ranging between -1.97 and -2.92 kJ mol...
متن کاملThe Halogen Bond in the Design of Functional Supramolecular Materials: Recent Advances
Halogen bonding is an emerging noncovalent interaction for constructing supramolecular assemblies. Though similar to the more familiar hydrogen bonding, four primary differences between these two interactions make halogen bonding a unique tool for molecular recognition and the design of functional materials. First, halogen bonds tend to be much more directional than (single) hydrogen bonds. Sec...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
دوره 6 شماره
صفحات -
تاریخ انتشار 2014