Protein–Ligand CH−π Interactions: Structural Informatics, Energy Function Development, and Docking Implementation
Authors:
Xiao, Yao; Woods, Robert J.
Affiliation:
Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia 30602, United States
Description:
Here, we develop an empirical energy function based on quantum mechanical data for the interaction between methane and benzene that captures the contribution from CH−π interactions. Such interactions are frequently observed in protein–ligand crystal structures, particularly for carbohydrate ligands, but have been hard to quantify due to the absence of a model for CH−π interactions in typical molecular mechanical force fields or docking scoring functions. The CH−π term was added to the AutoDock Vina (AD VINA) scoring function enabling its performance to be evaluated against a cohort of more than 1600 occurrences in 496 experimental structures of protein–ligand complexes. By employing a conformational grid search algorithm, inclusion of the CH−π term was shown to improve the prediction of the preferred orientation of flexible ligands in protein-binding sites and to enhance the detection of carbohydrate-binding sites that display CH−π interactions. Last but not least, this term was also shown to improve docking performance for the CASF-2016 benchmark set and a carbohydrate set.
Publications:
- Xiao, Yao; Woods, Robert J.; Protein–Ligand CH−π Interactions: Structural Informatics, Energy Function Development, and Docking Implementation; Journal of Chemical Theory and Computation, 2023
Tags:
Peptides and proteins ProteinRelated Projects:
No related projects available
Files:
| File Name | File Description | File Type | File Size | File URL |
|---|---|---|---|---|
| Supporting Information | Detected CH−π instances in the PDB including methyl groups; detected CH−π instances in the PDB excluding methyl groups; CH−π instances; result data for grid searching analysis; detected CH−π instances in the CASF-2016 benchmark set; result data for CASF-2016 docking analysis; detected CH−π instances in the carbohydrate set; and result data for carbohydrate docking analysis (XLSX) | xlsx | 441.76 KB | Login to download |
| Supporting Information | Histograms of the geometric quantities computed during CH−π detection; examples of CH−π interactions culled from the PDB involving the aromatic ring of PHE, HIS, TRP, and TYR, colored by AD VINA score (without CH−π); methane–benzene dimer interaction energy surfaces for the type B and C geometries at various vertical and horizontal distances and the corresponding histograms of the C-centroid horizontal offset values in the experimental structures; and rmsd (Å) versus empirical weighting factor (PDF) | 682.43 KB | Login to download |