A flexible approach for understanding protein stability.
A distance constraint model (DCM) is presented that identifies flexible regions within protein structure consistent with specified thermodynamic condition. The DCM is based on a rigorous free energy decomposition scheme representing structure as fluctuating constraint topologies. Entropy non-additivity is problematic for naive decompositions, limiting the success of heat capacity predictions. The DCM resolves non-additivity by summing over independent entropic components determined by an efficient network-rigidity algorithm. A minimal 3-parameter DCM is demonstrated to accurately reproduce experimental heat capacity curves. Free energy landscapes and quantitative stability-flexibility relationships are obtained in terms of global flexibility. Several connections to experiment are made.
Livesay
D R
DR
Department of Chemistry, California State Polytechnic University, Pomona, 3801 W Temple Ave, Pomona, CA 91768, USA.
Dallakyan
S
S
Wood
G G
GG
Jacobs
D J
DJ
D004355:Drug Stability; D019277:Entropy; D006860:Hydrogen Bonding; D008958:Models, Molecular; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D013314:Stress, Mechanical; D013816:Thermodynamics
D011506:Proteins