Understanding the α‐helix to coil transition in polypeptides using network rigidity: Predicting heat and cold denaturation in mixed solvent conditions

摘要: Thermodynamic stability in polypeptides is described using a novel Distance Constraint Model (DCM). Here, microscopic interactions are represented as constraints. A topological arrangement of constraints define mechanical framework. Each constraint the framework associated with an enthalpic and entropic contribution. All accessible arrangements distance form ensemble frameworks, each representing microstate polypeptide. partition function calculated exactly transfer matrix approach, where many respects DCM similar to Lifson-Roig model. The crucial difference that effect network rigidity explicitly for ensemble. Network interaction provides mechanism long-range molecular cooperativity enables proper treatment nonadditivity free energy decomposition. Accounting (1) helix 7 coil conformation changes along backbone model, (2) i 4 hydrogen-bond formation breaking Zimm-Bragg (3) structured unstructured solvent (hydration effects), six-parameter describes normal inverted helix- transitions polypeptides. Under suitable mixed conditions heat cold denaturation predicted. parameters fitted experimental data showing different degrees monomeric polypep- tides aqueous hexafluoroisopropanol (HFIP) solution at various HFIP concentrations. By assuming linear concentration dependence (up 6% by mole fraction) on model param- eters, all essential experimentally observed features captured. © 2004 Wiley Periodicals, Inc. Biopolymers 75: 1-31,