Evaluation of the Solvent Slaving Concept in Myoglobins Through the Use of Glassy and Sol-Gel Matrices

Functionally important protein dynamics come in a myriad of amplitudes and time scales which makes systematic studies challenging. The Solvent Slaving Model (SSM) orders protein dynamics based on the premise that protein motions are slaved to solvent motions with there being a hierarchy based on which solvent motions the specific protein dynamics are slaved(1, 2). The Protein Dynamic State Model (PDSM) is an extension of the SSM that defines dynamic states based on the temporal window during which specific solvent slaved dynamics are active(3, 4). Both models have yet to be tested systematically. In the present study, the activation energies (Ea's) for several functionally important dynamics are determined for a series of mutants of myoglobin as a function of different solvent matrices chosen to permit manipulation of specific solvent dynamics (e.g α and β relaxations). The matrices used include both trehalose glasses (β relaxations active but no α relaxations) and thin sol-gel films bathed in water/glycerol mixtures (both α and β relaxations active). The results show that for a diverse group of protein dynamics, including conformational averaging and side chain fluctuations and relaxations, the Ea's can be grouped into two broad categories: one with low Ea's (between 5 and 20 kJ/mol) and the other with much higher values (50-70 kJ/mol). The results expose how the time ordering for the onset of the functional influence of different dynamics is the result of the interplay between solvent dependent activation energy and the number of solvent slaved steps required to achieve the specific dynamical process.1. Frauenfelder, H. et al. (2009) ProcNatlAcadSci USA106, 5129-5134.2. Frauenfelder, H. et al. (2002) BiophysChem98, 35-48.3. Samuni, U. et al. (2007) Gene398, 234-248.4. Samuni, U. et al. (2007) JAmChemSoc129, 12756-12764.