title: Subangstrom accuracy in pHLA-I modeling by Rosetta FlexPepDock refinement protocol.
abstract: Flexible peptides binding to human leukocyte antigen (HLA) play a key role in mediating human immune responses and are also involved in idiosyncratic adverse drug reactions according to recent research. However, the structural determinations of pHLA complexes remain challenging under the present conditions. In this paper, the performance of a new peptide docking method, namely FlexPepDock, was systematically investigated by a benchmark of 30 crystallized structures of peptide-HLA class I complexes. The docking results showed that the near-native pHLA-I models with peptide bb-RMSD less than 2 Å were ranked in the top 1 model for 100% (70/70) docking cases, and the subangstrom models with peptide bb-RMSD less than 1 Å were ranked in the top 5 lowest-energy models for 65.7% (46/70) docking cases. Furthermore, 10 out of 70 docking cases ranked the subangstrom all-atom models in the top 5 lowest-energy models. The results showed that the FlexPepDock can generate high-quality models of pHLA-I complexes and can be widely applied to pHLA-I modeling and mechanism research of peptide-mediated immune responses.
authors: Key Laboratory of Biorheological Science and Technology (Ministry of Education), Chongqing University , Chongqing 400044, China.
authors: Tengfei
authors: T
authors: Liu
authors: Xianchao
authors: X
authors: Pan
authors: Li
authors: L
authors: Chao
authors: Wen
authors: W
authors: Tan
authors: Sujun
authors: S
authors: Qu
authors: Li
authors: L
authors: Yang
authors: Bochu
authors: B
authors: Wang
authors: Hu
authors: H
authors: Mei
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D015395:Histocompatibility Antigens Class I / Q000737:chemistry* / Q000276:immunology; D006801:Humans; D008024:Ligands; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000276:immunology; D011485:Protein Binding; D013816:Thermodynamics
chemical_list: D015395:Histocompatibility Antigens Class I; D008024:Ligands; D010455:Peptides