Quantum Calculation of Proton and Other Charge Transfer Steps in Voltage Sensing in the Kv1.2 Channel

• DOI: 10.1021/acs.jpcb.9b05448
• Publication Date: 2019-08-23T15:33:51Z
• Authors: Alisher M. Kariev; Michael E. Green
• Keywords: 0301 basic medicine; Water; Hydrogen Bonding; Molecular Dynamics Simulation; Arginine; Crystallography, X-Ray; Rats; 03 medical and health sciences; Kv1.2 Potassium Channel; Mutagenesis, Site-Directed; Animals; Quantum Theory; Protons

Ion channels in cell membranes control entry and exit of ions; their gating (opening closing) is key to functioning. It known that protons can pass through the voltage-sensing domain (VSD) such as Kv1.2. Quantum calculations for a section VSD show steps take responding voltage no major displacement protein backbone with change; 70 amino acids are included, 42 side chains (9 directly proton path), 28 only, 24 water molecules. Protons provide much current, capacitative current immediately preceding channel opening significant additional contributions from charge transfer other groups. Most models, contrast, require during gating. Energy terms without classical analogues (exchange plus correlation energy, which greater than thermal energy) quantum required. function leads to, approximately, correct opening. Calculated total (not only protons) reasonable compared experimental values. We also able account, at least qualitatively, two mutations, one curve left-shifted right-shifted, alternate paths required account these.