WFU Physics Colloquium

TITLE: Quantitative Stability/Flexibility Relationships (QSFR) within Protein Families

SPEAKER: Professor Dennis R. Livesay ,

TIME: Thursday Nov. 8, 2007 at 4:00 PM

PLACE: George P. Williams, Jr. Lecture Hall, (Olin 101)

Together with Don Jacobs (Department of Physics and Optical Science, UNC Charlotte), we are developing a powerful Distance Constraint Model (DCM) that harmoniously calculates stability and flexibility profiles within proteins^1,2. The DCM is an ensemble-based approach where each microstate is represented by a network rigidity topological framework from whence flexibility and rigidity information can be derived. Based on the underlying rigidity graphs, free energies are determined using a decomposition scheme that explicitly accounts for nonadditivity within entropy. Consequently, enthalpy-entropy compensation mechanisms are mechanistically linked through topology. Based on this unique union of mechanical and thermodynamic descriptions, the DCM is ideally suited for calculating Quantitative Stability/Flexibility Relationships (QSFR). QSFR is particularly useful when used in comparative studies³. For example, I will discuss comparative QSFR analyses of: (i.) ligated vs. unligated bacterial periplasmic binding proteins; (ii.) a mesophilic and thermophilic RNase H pair; and (iii.) a family of nine thioredoxins. Interestingly, at relative temperatures (i.e., Tm) protein stability and backbone flexibility are generally conserved in the latter two cases; however, cooperativity correlation, which is used to predict allosteric response, is highly variable. This work is supported by NIH R01 GM073082-01A1.

1.)Livesay et al. (2004). FEBS Lett, 576:468-476.
2.)Jacobs and Dallakayan (2005). Biophys J, 88:903-915.
3.)Livesay and Jacobs (2006). Proteins, 62:130-143.