We analyse the dynamics of near-extremal Reissner-Nordström black holes in asymptotically four-dimensional Anti de Sitter space (AdS 4 ). We work in the spherically symmetric approximation and study the thermodynamics and the response to a probe scalar field. We find that the behaviour of the system, at low energies and to leading order in our approximations, is well described by the Jackiw-Teitelboim (JT) model of gravity. In fact, this behaviour can be understood from symmetry considerations and arises due to the breaking of time reparametrisation invariance. The JT model has been analysed in considerable detail recently and related to the behaviour of the SYK model. Our results indicate that features in these models which arise from symmetry considerations alone are more general and present quite universally in near-extremal black holes.

Planar black holes in AdS have long-lived quasinormal modes which capture the physics of charge and momentum diffusion in the dual field theory. How should we characterize the effective dynamics of a probe system coupled to the conserved currents of the dual field theory? Specifically, how would such a probe record the long-lived memory of the black hole and its Hawking fluctuations? We address this question by exhibiting a universal gauge invariant framework which captures the physics of stochastic diffusion in holography: a designer scalar with a gravitational coupling governed by a single parameter, the Markovianity index. We argue that the physics of gauge and gravitational perturbations of a planar Schwarzschild-AdS black hole can be efficiently captured by such designer scalars. We demonstrate that this framework allows one to decouple, at the quadratic order, the long-lived quasinormal and Hawking modes from the short-lived ones. It furthermore provides a template for analyzing fluctuating open quantum field theories with memory. In particular, we use this set-up to analyze the diffusive Hawking photons and gravitons about a planar Schwarzschild-AdS black hole and derive the quadratic effective action that governs fluctuating hydrodynamics of the dual CFT. Along the way we also derive results relevant for probes of hyperscaling violating backgrounds at finite temperature.

We report on the use of large-scale distributed computing simulation and novel analysis techniques for examining the dynamics of a small protein. Matters addressed include folding rate, very long time scale kinetics, ensemble properties, and interaction with water. The target system for the study, the villin headpiece, has been of great interest to experimentalists and theorists both. Sampling totaled nearly 500 mus-the most extensive published to date for a system of villin's size in explicit solvent with all atom detail-and was in the form of tens of thousands of independent molecular dynamics trajectories, each several tens of nanoseconds in length. We report on kinetics sensitivity analyses that, using a set of short simulations, probed the role of water in villin's folding and sensitivity to the simulation's electrostatics treatment. By constructing Markovian state models (MSMs) from the collected data, we were able to propagate dynamics to times far beyond those directly simulated and to rapidly compute mean first passage times, long time kinetics (tens of microseconds), and evolution of ensemble property distributions over long times, otherwise currently impossible. We also tested our MSM by using it to predict the structure of villin de novo.

Although most experimental and theoretical studies of protein folding involve proteins in vitro, the effects of spatial confinement may complicate protein folding in vivo. In this study, we examine the folding dynamics of villin (a small fast folding protein) with explicit solvent confined to an inert nanopore. We have calculated the probability of folding before unfolding (Pfold) under various confinement regimes. Using Pfold correlation techniques, we observed two competing effects. Confining protein alone promotes folding by destabilizing the unfolded state. In contrast, confining both protein and solvent gives rise to a solvent-mediated effect that destabilizes the native state. When both protein and solvent are confined we see unfolding to a compact unfolded state different from the unfolded state seen in bulk. Thus, we demonstrate that the confinement of solvent has a significant impact on protein kinetics and thermodynamics. We conclude with a discussion of the implications of these results for folding in confined environments such as the chaperonin cavity in vivo.chaperonin mechanism ͉ explicit solvent ͉ distributed computing ͉ molecular dynamics H ow proteins fold into a unique native structure is an important unanswered question. There have been a number of experiments and computer simulations that have provided insight into the mechanism by which folding occurs (1, 2). Most of these experiments and simulations measure the dynamics of proteins in infinite dilution. However, bulk solvent is different from the cellular environment in which proteins truly fold. In vivo, protein dynamics occur in the context of the crowded cellular milieu and in confined spaces such as the chaperonin cavity, the proteosome, the ribosome exit tunnel, the translocon, etc. When considering these factors it is reasonable to assume that proteins may experience different energy landscapes when folding in vivo than in bulk, and these differences may constitute a significant piece of the folding puzzle.Confinement has been previously treated both analytically and via simulation using polymer physics models (3-10). These models predict that by excluding more extended structures confinement reduces the conformational entropy of the unfoldedstate ensemble. This restriction leads to the relative stabilization of the folded state. These models are in qualitative accord with recent experiments that have shown accelerated folding of small proteins in chaperonin mutants possessing decreased cavity volume (11). Despite the elegance and intuitiveness of these models, they omit details that may be important when thinking of folding in vivo.For example, it is known that solvent plays a critical role in protein folding, as most of the free energy for folding comes from maximizing solvent entropy (because of the molecular nature of hydrophobicity). Polymer models for confined folding do not consider the effect of confinement on the solvent and its subsequent effects on protein stability. Although explicit solvent complicates analytical models a...