Identifying Two-State Transitions by Microcanonical Analysis: Coarse-Grained Simulations of Helical Peptides

摘要: Two-state folding is an important feature in protein thermodynamics. It describes the transition between a native and denatured state without intermediates that are populated at equilibrium. A widely used test for two-state calorimetric criterion which probes features canonical specific heat curve. However, this does not suffice to identify [Zhou et al., Protein Science, 8 (1999)]. Nevertheless, microcanonical analysis, where density of states directly measured, can provide unambiguous information about nature transition.In work, we use generalized-ensemble simulations calculate simplified implicit solvent, four bead per amino acid coarse-grained model biased protein's state. The thermodynamics different helical peptides studied. Our results show strong correlations energetics temperature structural rearrangements state: as chain length increases, helix breaks into bundles tertiary contacts become important. Statistical models have suggested cooperativity arises from interplay secondary interactions (e. g. [Ghosh Dill, JACS, 131, 2306 (2009)]). corroborate picture: only sequence stabilize well-defined hydrophobic core bundle will exhibit first-order like transition. We illustrate by performing analysis 73-residue long de novo three-helix bundle.