Mutant analysis of Kcng4b reveals how the different functional states of the voltage-gated potassium channel regulate ear development.

The voltage gated (Kv) slow-inactivating delayed rectifier channel regulates the development of hollow organs of the zebrafish. The functional channel consists of the tetramer of electrically active Kcnb1 (Kv2.1) subunits and Kcng4b (Kv6.

Low-Barrier Hydrogen Bond Determines Target-Binding Affinity and Specificity of the Antitubercular Drug Bedaquiline.

The role of short strong hydrogen bonds (SSHBs) in ligand-target binding remains largely unexplored, thereby hindering a potentially important avenue in rational drug design. Here we investigate the interaction between the antituberculosis drug bedaquiline (Bq) and the mycobacterial ATP synthase to unravel the role of a specific hydrogen bond to a conserved acidic residue in the target affinity and specificity. Our ab initio molecular dynamics simulations reveal that this bond belongs to the SSHB category and accounts for a substantial fraction of the target binding free energy.

Coevolution-Driven Method for Efficiently Simulating Conformational Changes in Proteins Reveals Molecular Details of Ligand Effects in the β2AR Receptor.

With the advent of AI-powered structure prediction, the scientific community is inching closer to solving protein folding. An unresolved enigma, however, is to accurately, reliably, and deterministically predict alternative conformational states that are crucial for the function of, e.g.

Molecular mechanism and energetics of coupling between substrate binding and product release in the F-ATPase catalytic cycle.

F-ATPase is a motor protein that couples the rotation of its rotary [Formula: see text] subunit with ATP synthesis or hydrolysis. Single-molecule experiments indicate that nucleotide binding and release events occur almost simultaneously during the synthesis cycle, allowing the energy gain due to spontaneous binding of ADP to one catalytic [Formula: see text] subunit to be directly harnessed for driving the release of ATP from another rather than being dissipated as heat. Here, we examine the unknown mechanism of this coupling that is critical for an exceptionally high mechanochemical efficiency of F-ATPase by means of all-atom free-energy simulations.