News
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 moreStatistical 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 moreDynamical phase transitions reveal amyloid-like states on protein folding landscapes
Developing an understanding of protein misfolding processes presents a crucial challenge for unlocking the mysteries of human disease. In this article, we present our observations of β-sheet-rich misfolded states on a number of protein dynamical landscapes investigated through molecular dynamics simulation and Markov state models. We employ a nonequilibri…
Read moreComplex pathways in folding of protein G explored by simulation and experiment
The B1 domain of protein G has been a classic model system of folding for decades, the subject of numerous experimental and computational studies. Most of the experimental work has focused on whether the protein folds via an intermediate, but the evidence is mostly limited to relatively slow kinetic observations with a few structural probes. In this work we ob…
Read morePerspective: 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 moreMarkov state models provide insights into dynamic modulation of protein function
CONSPECTUS: Protein function is inextricably linked to protein dynamics. As we move from a static structural picture to a dynamic ensemble view of protein structure and function, novel computational paradigms are required for observing and understanding conformational dynamics of proteins and its functional implications. In principle, molecular dynamics simula…
Read moreThe 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 morePercolation-like phase transitions in network models of protein dynamics
In broad terms, percolation theory describes the conditions under which clusters of nodes are fully connected in a random network. A percolation phase transition occurs when, as edges are added to a network, its largest connected cluster abruptly jumps from insignificance to complete dominance. In this article, we apply percolation theory to meticulously const…
Read moreFree energy landscape of activation in a signalling protein at atomic resolution
The interconversion between inactive and active protein states, traditionally described by two static structures, is at the heart of signalling. However, how folded states interconvert is largely unknown due to the inability to experimentally observe transition pathways. Here we explore the free energy landscape of the bacterial response regulator NtrC by comb…
Read more