RESUMEN

Human aquaporin 4 has been studied using molecular dynamics (MD) simulations in the absence and presence of pulses of external static electric fields. The pulses were 10 ns in duration and 0.012-0.065 V/Å in intensity acting along both directions perpendicular to the pores. Water permeability and the dipolar response of all residues of interest (including the selectivity filter) within the pores have been studied. Results showed decreased levels of water osmotic permeability within aquaporin channels during orthogonally-oriented field impulses, although care must be taken with regard to statistical certainty. This can be explained observing enhanced "dipolar flipping" of certain key residues, especially serine 211, histidine 201, arginine 216, histidine 95 and cysteine 178. These residues are placed at the extracellular end of the pore (serine 211, histidine 201, and arginine 216) and at the cytoplasm end (histidine 95 and cysteine 178), with the key role in gating mechanism, hence influencing water permeability.

Asunto(s)

Acuaporina 4/química , Simulación de Dinámica Molecular , Agua/química , Electricidad , Humanos , Modelos Moleculares , Conformación Proteica

RESUMEN

Water has many intriguing and anomalous physical properties that have puzzled and titillated the scientific community for centuries, perhaps none more so than the proposition that water may retain some (permanent) "memory" of conditions (e.g., dilution) or electric fields to which it has been subject. Here, we have performed non-equilibrium molecular dynamics simulations of liquid water in external electric-field nanosecond pulses, at 260-310 K, and gauged significant non-thermal field effects in terms of dipolar response. Response of both system- and individual-dipoles has been investigated, and autocorrelation functions of both show more significant effects in stronger fields, with more sluggish relaxation. Crucially, we show that once the field is removed, the dipoles relax, exhibiting no memory or permanent dipolar alignment. We also quantify the time scales for system dynamical-dipolar properties to revert to zero-field equilibrium behaviour.