66 research outputs found
Discovering Conformational Sub-States Relevant to Protein Function
Background: Internal motions enable proteins to explore a range of conformations, even in the vicinity of native state. The role of conformational fluctuations in the designated function of a protein is widely debated. Emerging evidence suggests that sub-groups within the range of conformations (or sub-states) contain properties that may be functionally relevant. However, low populations in these sub-states and the transient nature of conformational transitions between these substates present significant challenges for their identification and characterization. Methods and Findings: To overcome these challenges we have developed a new computational technique, quasianharmonic analysis (QAA). QAA utilizes higher-order statistics of protein motions to identify sub-states in the conformational landscape. Further, the focus on anharmonicity allows identification of conformational fluctuations that enable transitions between sub-states. QAA applied to equilibrium simulations of human ubiquitin and T4 lysozyme reveals functionally relevant sub-states and protein motions involved in molecular recognition. In combination with a reaction pathway sampling method, QAA characterizes conformational sub-states associated with cis/trans peptidyl-prolyl isomerization catalyzed by the enzyme cyclophilin A. In these three proteins, QAA allows identification of conformational sub-states, with critical structural and dynamical features relevant to protein function. Conclusions: Overall, QAA provides a novel framework to intuitively understand the biophysical basis of conformational diversity and its relevance to protein function. © 2011 Ramanathan et al
Back-action Evading Measurements of Nanomechanical Motion
When performing continuous measurements of position with sensitivity
approaching quantum mechanical limits, one must confront the fundamental
effects of detector back-action. Back-action forces are responsible for the
ultimate limit on continuous position detection, can also be harnessed to cool
the observed structure, and are expected to generate quantum entanglement.
Back-action can also be evaded, allowing measurements with sensitivities that
exceed the standard quantum limit, and potentially allowing for the generation
of quantum squeezed states. We realize a device based on the parametric
coupling between an ultra-low dissipation nanomechanical resonator and a
microwave resonator. Here we demonstrate back-action evading (BAE) detection of
a single quadrature of motion with sensitivity 4 times the quantum zero-point
motion, back-action cooling of the mechanical resonator to n = 12 quanta, and a
parametric mechanical pre-amplification effect which is harnessed to achieve
position resolution a factor 1.3 times quantum zero-point motion.Comment: 19 pages (double-spaced) including 4 figures and reference
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