Paper Citing NAMD - Abstract
Reale, Riccardo; English, Niall J.; Garate, Jose-Antonio; Marracino, Paolo; Liberti, Micaela; Apollonio, Francesca
Human aquaporin 4 gating dynamics under and after nanosecond-scale static and alternating electric-field impulses: A molecular dynamics study of field effects and relaxation
JOURNAL OF CHEMICAL PHYSICS, 139 Art. No. 205101, NOV 28 2013
Water self-diffusion and the dipolar response of the selectivity filter within human aquaporin 4 have been studied using molecular dynamics (MD) simulations in the absence and presence of pulses of external static and alternating electric fields. The pulses were approximately 50 and 100 ns in duration and 0.0065 V/angstrom in (r.m.s.) intensity and were either static or else 2.45 or 100 GHz in frequency and applied both along and perpendicular to the channels. In addition, the relaxation of the aquaporin, water self-diffusion and gating dynamics following cessation of the impulses was studied. In previous work it was determined that switches in the dihedral angle of the selectivity filter led to boosting of water permeation events within the channels, in the presence of identical external static and alternating electric fields, although applied continuously. Here the application of field impulses (and subsequently, upon removal) has shown that it is the dipolar orientation of the histidine-201 residue in the selectivity filter which governs the dihedral angle, and hence influences water self-diffusion; this constitutes an appropriate order parameter. The dipolar response of this residue to the applied field leads to the adoption of four distinct states, which we modelled as time-homogeneous Markov jump processes, and may be distinguished in the potential of mean force (PMF) as a function of the dipolar orientation of histidine-201. The observations of enhanced "dipolar flipping" of H201 serve to explain increased levels of water self-diffusion within aquaporin channels during, and immediately following, field impulses, although the level of statistical certainty here is lower. Given the appreciable size of the energy barriers evident in PMFs computed directly from deterministic MD (whether in the absence or presence of external fields), metadynamics calculations were undertaken to explore the free-energy landscape of histidine-201 orientation with greater accuracy and precision. These indicate that electric fields do alter the free-energy profile of the H201 side-chain orientation, wherein a perturbation of the symmetric bimodal state evident in the zero-field case is observed. These effects are dependent on the field intensities. (C) 2013 AIP Publishing LLC.
