title: Controlling dissociation channels of gas-phase protein complexes using charge manipulation.
abstract: Coarse-grained simulations with charge hopping were performed for a positively charged tetrameric transthyretin (TTR) protein complex with a total charge of +20. Charges were allowed to move among basic amino acid sites as well as N-termini. Charge distributions and radii of gyration were calculated for complexes simulated at two temperatures, 300 and 600 K, under different scenarios. One scenario treated the complex in its normal state allowing charge to move to any basic site. Another scenario blocked protonation of all the N-termini except one. A final scenario used the complex in its normal state but added a basic-site containing tether (charge tag) near the N-terminus of one chain. The differences in monomer unfolding and charging were monitored in all three scenarios and compared. The simulation results show the importance of the N-terminus in leading the unfolding of the monomer units; a process that follows a zipper-like mechanism. Overall, experimentally modifying the complex by adding a tether or blocking the protonation of N-termini may give the potential for controlling the unraveling and subsequent dissociation of protein complexes.
authors: Department of Chemistry, University of British Columbia, Vancouver, BC, V6T 1Z1, Canada.
authors: Sarah K
authors: SK
authors: Fegan
authors: Mark
authors: M
authors: Thachuk
mesh_terms: D019943:Amino Acid Substitution; D006358:Hot Temperature; D006801:Humans; D055767:Immobilized Proteins / Q000737:chemistry / Q000235:genetics; D007700:Kinetics; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D009010:Monte Carlo Method; D050505:Mutant Proteins / Q000737:chemistry; D011228:Prealbumin / Q000737:chemistry* / Q000235:genetics; D021382:Protein Sorting Signals; D020836:Protein Structure, Quaternary; D058767:Protein Unfolding; D013499:Surface Properties; D014835:Volatilization
chemical_list: D055767:Immobilized Proteins; D050505:Mutant Proteins; D011228:Prealbumin; D021382:Protein Sorting Signals