Quantum Calculations on Ion Channels: Why Are They More Useful Than Classical Calculations, and for Which Processes Are They Essential?

Abstract

There are reasons to consider quantum calculations to be necessary for ion channels, for two types of reasons. The calculations must account for charge transfer, and the possible switching of hydrogen bonds, which are very difficult with classical force fields. Without understanding charge transfer and hydrogen bonding in detail, the channel cannot be understood. Thus, although classical approximations to the correct force fields are possible, they are unable to reproduce at least some details of the behavior of a system that has atomic scale. However, there is a second class of effects that is essentially quantum mechanical. There are two types of such phenomena: exchange and correlation energies, which have no classical analogues, and tunneling. Tunneling, an intrinsically quantum phenomenon, may well play a critical role in initiating a proton cascade critical to gating. As there is no classical analogue of tunneling, this cannot be approximated classically. Finally, there are energy terms, exchange and correlation energy, whose values can be approximated classically, but these approximations must be subsumed within classical terms, and as a result, will not have the correct dependence on interatomic distances. Charge transfer, and tunneling, require quantum calculations for ion channels. Some results of quantum calculations are shown.

Sodium and Magnesium Ion Location at the Backbone and at the Nucleobase of RNA: Ab Initio Molecular Dynamics in Water Solution

“…The interactions of Na + or Mg 2+ ions with the guanine base in water solution exhibited differential distributions of the conical angle between the ionic bond and the carbonyl group, indicating distinct types of hybridization of the latter as a possible cause of the modified interaction of guanine in RNA secondary or tertiary structures for varying Na + and Mg 2+ electrolyte composition. , In addition, the typical ranges of the angles C–O–Na/Mg obtained in our simulations in water media suggest somewhat different regions compared to the ranges reported for the crystal structures . These results support the interpretation that the differential effects of Na + and Mg 2+ ions upon the RNA structure may have dynamic origin and arise due to different abilities of the two types of ions to coordinate oxygen atoms, support their inner hydration shells, and move in the water solvent. ,, The observed 100 ps-long periods of thermal stability of the inner hydration shell of Mg 2+ ions, with brief subpicosecond exchange of water molecules, further suggest that the Mg 2+ -RNA interaction may also involve purely quantum phenomena such as tunneling through potential barriers, in addition to the classical over-the-barrier thermal transition. , This means that quantum tunneling may speed up certain conformational transitions that would otherwise need higher classical driving potentials and extended periods of thermal agitation. , …”

“…79,80 This means that quantum tunneling may speed up certain conformational transitions that would otherwise need higher classical driving potentials and extended periods of thermal agitation. 81,82 The versatility of the RNA structure and function is intertwined with the chemical fragility of RNA. 83−85 The ability of divalent cations such as Mg 2+ to stabilize the RNA structure is pertinent to molecular biology research and synthesis of novel therapeutic agents, including RNA vaccines.…”

“… 79 , 80 This means that quantum tunneling may speed up certain conformational transitions that would otherwise need higher classical driving potentials and extended periods of thermal agitation. 81 , 82 …”

Thermal stability of solitons in protein $α$-helices

“…Thus, the solitons can reach 4-5 times faster the opposite α-helix end where they can be absorbed or suffer amplitude loss during bouncing. Consequently, the lifetime of the soliton as measured in globular proteins might not be indicative of the lifetime in any longer α-helices, such as those found in transmembrane proteins or in ion channels [45,46].…”

Quantum propensities in the brain cortex and free will

“…Similarly to the Stern-Gerlach experiment discussed above, the environment would be able to measure alternative (incompatible) quantum observables of neurons, which would comprise a set of functional conformations of neural biomolecules with catalytic activities. For example, quantum chemistry research supports dynamic quantum effects such as quantum tunneling in the gating of voltage-gated ion channels [58][59][60][61] or in the zipping of SNARE proteins during neurotransmitter release [38,62].…”