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Molecular dynamics simulations of the K+ channel from Streptomyces lividans (KcsA channel) were performed in a membrane-mimetic environment with Na+ and K+ in different initial locations. The structure of the channel remained stable and well preserved for simulations lasting up to 1.5 ns. Salt bridges between Asp80 and Arg89 of neighboring subunits, not(More)
Current all-atom potential based molecular dynamics (MD) allows the identification of a protein's functional motions on a wide-range of timescales, up to few tens of nanoseconds. However, functional, large-scale motions of proteins may occur on a timescale currently not accessible by all-atom potential based MD. To avoid the massive computational effort(More)
In the brain, high cognitive functions are encoded by coherent network oscillations. Key players are inhibitory interneurons that, by releasing GABA into principal cells, pace targeted cells. Among these, oriens-lacunosum moleculare (O-LM) interneurons that provide a theta frequency patterned output to distal dendrites of pyramidal cells are endowed with(More)
Extracellular tetraethylammonium (TEA+) inhibits the current carried out by K+ ions in potassium channels. Structural models of wild-type (WT) and Y82C KcsA K+ channel/TEA+ complexes are here built using docking procedures, electrostatics calculations and molecular dynamics simulations. The calculations are based on the structure determined by Doyle et al.(More)
The interplay between dopamine and alpha-synuclein (AS) plays a central role in Parkinson's disease (PD). PD results primarily from a severe and selective devastation of dopaminergic neurons in substantia nigra pars compacta. The neuropathological hallmark of the disease is the presence of intraneuronal proteinaceous inclusions known as Lewy bodies within(More)
Prion propagation in transmissible spongiform encephalopathies involves the conversion of the cellular prion protein, PrPC, into the pathogenic conformer PrPSc. Human familial forms of the disease are linked to specific mutations in the PrP gene, PRNP, and include Gerstmann-Strussler-Scheinker syndrome (GSS), familial Creutzfeldt-Jakob disease (fCJD), and(More)
Molecular dynamics simulations and electrostatic modeling are used to investigate structural and dynamical properties of the potassium ions and of water molecules inside the KcsA channel immersed in a membrane-mimetic environment. Two potassium ions, initially located in the selectivity filter binding sites, maintain their position during 2 ns of dynamics.(More)
HCN channels are activated by membrane hyperpolarization and regulated by cyclic nucleotides, such as cyclic adenosine-mono-phosphate (cAMP). Here we present structural models of the pore region of these channels obtained by using homology modeling and validated against spatial constraints derived from electrophysiological experiments. For the construction(More)
Peptides related to the N-terminal region of calcitonin gene-related peptide (CGRP) were tested for their ability to modulate neuronal nicotinic acetylcholine receptors (nAChRs) of rat cultured chromaffin cells under whole cell patch-clamp conditions. Although CGRP(1-7) and CGRP(2-7) depressed responses mediated by nAChRs, CGRP(1-6), CGRP(1-5), or CGRP(1-4)(More)
Humans' bitter taste perception is mediated by the hTAS2R subfamily of the G protein-coupled membrane receptors (GPCRs). Structural information on these receptors is currently limited. Here we identify residues involved in the binding of phenylthiocarbamide (PTC) and in receptor activation in one of the most widely studied hTAS2Rs (hTAS2R38) by means of(More)