Toward an Improved Understanding of the Dissociation Mechanism of Gas Phase Protein Complexes.

Understanding the dissocn. mechanism of multimeric protein complex ions is important for deciphering gas phase dissocn. expts. The dissocn. of cytochrome c’ dimer ions in the gas phase was investigated in the present study by constrained mol. dynamics simulations. The center of mass (COM) distance between two monomers was selected as the constrained coordinate. The no. of intermol. hydrogen bonds, smallest distance of intermol. residuals, value of dipole moments, root-mean-square deviations, and potential energy components of the force field as a function of COM distance were examd. for different charge partitionings of the +10 total charge state. These data were rationalized with free energy profiles to produce a qual. description of the dissocn. process. When charges are sym. distributed between the monomers in the dimer, dissocn. occurs at a well-defined distance with only small structural changes in the monomers. There is an elastic type of stretching that initially resists the sepn. of the monomers but after dissocn. the monomers recoil slightly from this and relax. For asym. distributed charges, the dissocn. event is not nearly as well-defined because the more highly charged monomer unfolds before dissocn. occurs. It is found in almost all cases, a charged N-terminus tethers this unfolding monomer to its dimer partner by binding in a nonspecific manner. This helps encourage monomer unfolding in the dissocn. pathway. It is also shown that while the intermol. Coulomb repulsion between the monomers is not the largest contribution to the overall potential energy, it dominates the potential energy difference between different charge states. [on SciFinder(R)]