The ChEMBL database was mined to efficiently assemble an ion channel-focused screening library. The compiled library consists of 3241 compounds representing 123 templates across nine ion channel categories. Compounds in the screening library are annotated with their respective ion channel category to facilitate back-tracing of prospective molecular targets from phenotypic screening results. The...

A hierarchical computational strategy combining molecular modeling, electrostatics calculations, molec-ular dynamics, and Brownian dynamics simulations is developed and implemented to compute electrophysiologicallymeasurable properties of the KcsA potassium channel. Models for a series of channels with different pore sizes aredeveloped from the known x-ray structure, using insights ...

Ion channel gating kinetics can be described using Kramers' diffusion theory of reaction rates between several closed and open states, where transition rates between states depend exponentially on the membrane potential V. It has been suggested that transition rates have a more complex dependence on V at voltage extremes, but this has never been quantified. We measured the rate constant of the ...

The plasma wave acceleration of electron in the bubble regime is investigated in a new configuration containing a planar wiggler. The space-charge field of the laser-created ion channel can focuse and stabilize the electron trajectory to guide it toward the acceleration region. The high-gradient plasma wave field can resonantly accelerate the trapped electron to higher energies in the presence ...

Calmodulin (CaM) is a ubiquitous intracellular calcium sensor that directly binds to and modulates a wide variety of ion channels. Despite the large repository of high-resolution structures of CaM bound to peptide fragments derived from ion channels, there is no structural information about CaM bound to a fully folded ion channel at the plasma membrane. To determine the location of CaM docked t...

Ion channel receptors are a vital component of nervous system signaling, allowing rapid and direct conversion of a chemical neurotransmitter message to an electrical current. In recent decades, it has become apparent that ionotropic receptors are regulated by protein-protein interactions with other ion channels, G-protein coupled receptors and intracellular proteins. These other proteins can al...

Rate-equilibrium free energy relationship (REFER) analysis provides information on transition-state structures and has been applied to reveal the temporal sequence in which the different regions of an ion channel protein move during a closed-open conformational transition. To date, the theory used to interpret REFER relationships has been developed only for equilibrium mechanisms. Gating of mos...

Ryanodine receptors (RyRs), intracellular calcium release channels required for cardiac and skeletal muscle contraction, are macromolecular complexes that include kinases and phosphatases. Phosphorylation/dephosphorylation plays a key role in regulating the function of many ion channels, including RyRs. However, the mechanism by which kinases and phosphatases are targeted to ion channels is not...

An anomalous diffusion model for ion channel gating is put forward. This scheme is able to describe nonexponential, power-law-like distributions of residence time intervals in several types of ion channels. Our method presents a generalization of the discrete diffusion model by Millhauser, Salpeter, and Oswald [Proc. Natl. Acad. Sci. U.S.A. 85, 1503 (1988)] to the case of a continuous, anomalou...

Research that has focused on external representations in biochemistry has uncovered student difficulties in comprehending and interpreting external representations. This study focuses on students' understanding of three external representations (ribbon diagram, wireframe, and hydrophobic/hydrophilic) of the potassium ion channel protein. Analysis of the interview data demonstrates that students...