title: Molecular simulations to determine the chelating mechanisms of various metal ions to the His-tag motif: a preliminary study.
abstract: In the present study, molecular simulations were performed to investigate the chelating mechanisms of various metal ions to the His-tag motifs with various His residues. The chelation mostly involved the i and i+2 His residues for Ni(2+), Zn(2+), Cu(2+), and Co(2+), while the cooperation of 3 His residues was necessary when Fe(3+) was involved in chelation with His-tags having more than 4 His residues. Metal ion was best fitted into the pocket formed by the imidazole nitrogens while it was about equally located among these nitrogen atoms. His-tag6 was found to have little effect on the structural integrity while the target protein contains more than 68 amino acid residues. Ni(2+) interacted with the imidazole nitrogen of His3 in the beginning of chelation, and then entered into the pocket formed by His3 and His5 at 4 ns during the 10 ns molecular dynamics simulations. The fast chelating process resulted in successful application of IMAC techniques in efficient protein purification.
authors.affiliation: Department of Chemical Engineering, National Taipei University of Technology, No. 1 Sec. 3 Chung-Hsiao E. Rd., Taipei 10643, Taiwan. f10894@ntut.edu.tw
authors.forename: Hsuan-Liang
authors.initials: HL
authors.lastname: Liu
authors.forename: Yih
authors.initials: Y
authors.lastname: Ho
authors.forename: Chia-Ming
authors.initials: CM
authors.lastname: Hsu
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000619:Aminohydrolases / Q000737:chemistry; D000818:Animals; D001234:Aspergillus niger / Q000737:chemistry; D002614:Chelating Agents / Q000737:chemistry*; D002645:Chickens; D002846:Chromatography, Affinity; D003198:Computer Simulation; D020224:Expressed Sequence Tags / Q000737:chemistry; D006639:Histidine / Q000737:chemistry*; D007093:Imidazoles / Q000378:metabolism; D007477:Ions / Q000737:chemistry*; D007700:Kinetics; D008024:Ligands; D019216:Metals, Heavy / Q000378:metabolism*; D008958:Models, Molecular; D026902:Potassium Channel Blockers / Q000737:chemistry; D012231:Rhizobium; D012605:Scorpions; D014118:Toxins, Biological / Q000737:chemistry
chemical_list: D002614:Chelating Agents; D007093:Imidazoles; D007477:Ions; D008024:Ligands; D019216:Metals, Heavy; D026902:Potassium Channel Blockers; D014118:Toxins, Biological; D006639:Histidine; D000619:Aminohydrolases