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There are several examples of membrane-associated protein domains that target curved membranes. This behavior is believed to have functional significance in a number of essential pathways, such as clathrin-mediated endocytosis, which involve dramatic membrane remodeling and require the recruitment of various cofactors at different stages of the process.(More)
Assessing the convergence of a biomolecular simulation is an essential part of any careful computational investigation, because many fundamental aspects of molecular behavior depend on the relative populations of different conformers. Here we present a physically intuitive method to self-consistently assess the convergence of trajectories generated by(More)
We used all-atom molecular dynamics simulations to investigate the structure and properties of the actin filament, starting with either the recent Oda model or the older Holmes model. Simulations of monomeric and polymerized actin show that polymerization changes the nucleotide-binding cleft, bringing together the Q137 side chain and bound ATP in a way that(More)
We extend replica-exchange simulation in two ways and apply our approaches to biomolecules. The first generalization permits exchange simulation between models of differing resolution--i.e., between detailed and coarse-grained models. Such "resolution exchange" can be applied to molecular systems or spin systems. The second extension is to "pseudoexchange"(More)
Molecular dynamics simulations of the A(2A) adenosine receptor totaling 1.4 μs show clear evidence for specific sites mediating interactions between adenosine-bound A(2A) and cholesterol. The strongest evidence is for three binding sites. Two are in the extracellular leaflet, with one site interacting with helices VII and I, and the other with helices II(More)
An overall multiscale simulation strategy for large scale coarse-grain simulations of membrane protein systems is presented. The protein is modeled as a heterogeneous elastic network, while the lipids are modeled using the hybrid analytic-systematic (HAS) methodology, where in both cases atomistic level information obtained from molecular dynamics(More)
The function of G-protein-coupled receptors is tightly modulated by the lipid environment. Long-timescale molecular dynamics simulations (totaling approximately 3 mus) of the A(2A) receptor in cholesterol-free bilayers, with and without the antagonist ZM241385 bound, demonstrate the instability of helix II in the apo receptor in cholesterol-poor membrane(More)
Molecular dynamics simulations reveal substructures within the liquid-ordered phase of lipid bilayers. These substructures, identified in a 10 μs all-atom trajectory of liquid-ordered/liquid-disordered coexistence (L(o)/L(d)) are composed of saturated hydrocarbon chains packed with local hexagonal order and separated by interstitial regions enriched in(More)
Functioning as key players in cellular regulation of membrane curvature, BAR domain proteins bend bilayers and recruit interaction partners through poorly understood mechanisms. Using electron cryomicroscopy, we present reconstructions of full-length endophilin and its N-terminal N-BAR domain in their membrane-bound state. Endophilin lattices expose large(More)
Mesoscopic simulations and electron microscopy of N-BAR domain-induced liposome remodeling are used to characterize the process of liposome tubulation and vesiculation. The overall process of membrane remodeling is found to involve complex couplings among the N-BAR protein density, the degree of N-BAR oligomerization, and the membrane density. A comparison(More)