Free energy barrier estimation for the dissociation of charged protein complexes in the gas phase.
Free energies are calculated for the protonated cytochrome c' dimer ion in the gas phase as a function of the center of mass distance between the monomers. A number of different charge partitionings are examined as well as the behavior of the neutral complex. It is found that monomer unfolding competes with complex dissociation and that the relative importance of these two factors depends upon the charge partitioning in the complex. Symmetric charge partitionings preferentially suppress the dissociation barrier relative to unfolding, and complexes tend to dissociate promptly with little structural changes occurring in the monomers. Alternatively, asymmetric charge partitionings preferentially lower the barrier for monomer unfolding relative to the dissociation barrier. In this case, the monomer with the higher charge unfolds before the complex dissociates. For the homodimer considered here, this pathway has a large free energy barrier. The results can be rationalized using schematic two-dimensional free energy surfaces. Additionally, for large multimeric complexes, it is argued that the unfolding and subsequent charging of a single monomer is a favorable process, cooperatively lowering both the unfolding and dissociation barriers at the same time.
Wanasundara
Surajith N
SN
Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, BC, V6T 1Z1, Canada.
Thachuk
Mark
M
D045304:Cytochromes c / Q000737:chemistry*; D005740:Gases / Q000737:chemistry*; D008958:Models, Molecular; D011485:Protein Binding; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D013816:Thermodynamics
D005740:Gases; D045304:Cytochromes c