Probing the origins of two-state folding

Many protein systems fold in a two-state manner. Random models, however, rarely display two-state kinetics and thus such behavior should not be accepted as a default. While theories for the prevalence of two-state kinetics have been presented, none sufficiently explain the breadth of experimental observations. A model, making minimal assumptions, is introduced…

Read more

Chemical kinetics and mechanisms of complex systems: a perspective on recent theoretical advances

This Perspective presents a personal overview of the current status of the theory of chemical kinetics and mechanisms for complex processes. We attempt to assess the status of the field for reactions in the gas phase, at gas-solid interfaces, in liquid solutions, in enzymes, and for protein folding. Some unifying concepts such as potential energy surfaces, fre…

Read more

A molecular interpretation of 2D IR protein folding experiments with Markov state models

The folding mechanism of the N-terminal domain of ribosomal protein L9 (NTL91-39) is studied using temperature-jump (T-jump) amide I’ two-dimensional infrared (2D IR) spectroscopy in combination with spectral simulations based on a Markov state model (MSM) built from millisecond-long molecular dynamics trajectories. The results provide evidence for a compact w…

Read more

Statistical model selection for Markov models of biomolecular dynamics

Markov state models provide a powerful framework for the analysis of biomolecular conformation dynamics in terms of their metastable states and transition rates. These models provide both a quantitative and comprehensible description of the long-time scale dynamics of large molecular dynamics with a Master equation and have been successfully used to study prot…

Read more

Perspective: Markov models for long-timescale biomolecular dynamics

Molecular dynamics simulations have the potential to provide atomic-level detail and insight to important questions in chemical physics that cannot be observed in typical experiments. However, simply generating a long trajectory is insufficient, as researchers must be able to transform the data in a simulation trajectory into specific scientific insights. Alth…

Read more

The dynamic conformational cycle of the group I chaperonin C-termini revealed via molecular dynamics simulation

Chaperonins are large ring shaped oligomers that facilitate protein folding by encapsulation within a central cavity. All chaperonins possess flexible C-termini which protrude from the equatorial domain of each subunit into the central cavity. Biochemical evidence suggests that the termini play an important role in the allosteric regulation of the ATPase cycle…

Read more