title: Molecular recognition of Fc-specific ligands binding onto the consensus binding site of IgG: insights from molecular simulation.
abstract: Immunoglobulin G (IgG) plays an important role in clinical diagnosis and therapeutics. Meanwhile, the consensus binding site (CBS) on the Fc domain of IgG is responsible for ligand recognition, especially for Fc-specific ligands. In this study, molecular simulation methods were used to investigate molecular interactions between the CBS of the Fc domain and seven natural Fc-specific ligands. The analysis on the binding energy of the Fc-ligand complex indicated that hydrophobic interactions provide the main driving force for the Fc-ligand binding processes. The hot spots on the ligands and Fc were identified with the computational alanine scanning approach. It was found that the residues of tryptophan and tyrosine on the ligands have significant contributions for the Fc-ligand binding, while Met252, Ile253, Asn434, His435, and Tyr436 are the key residues of Fc. Moreover, two binding modes based on tryptophan or tyrosine were summarized and constructed according to the pairwise interaction analysis. Guidelines for the rational design of CBS-specific ligands with high affinity and specificity were proposed.
authors.affiliation: State Key Laboratory of Chemical Engineering, Department of Chemical and Biological Engineering, Zhejiang University, Hangzhou, 310027, China.
authors.forename: Hong-Fei
authors.initials: HF
authors.lastname: Tong
authors.forename: Dong-Qiang
authors.initials: DQ
authors.lastname: Lin
authors.forename: Qi-Lei
authors.initials: QL
authors.lastname: Zhang
authors.forename: Rong-Zhu
authors.initials: RZ
authors.lastname: Wang
authors.forename: Shan-Jing
authors.initials: SJ
authors.lastname: Yao
mesh_terms: D001665:Binding Sites; D003198:Computer Simulation; D007074:Immunoglobulin G / Q000737:chemistry*; D008024:Ligands; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D020539:Sequence Analysis, Protein; D014364:Tryptophan / Q000737:chemistry / Q000502:physiology; D014443:Tyrosine / Q000737:chemistry / Q000502:physiology
chemical_list: D007074:Immunoglobulin G; D008024:Ligands; D014443:Tyrosine; D014364:Tryptophan
keywords: Fc-specific ligand; IgG; affinity; molecular recognition; molecular simulation