Emerging Concepts in Ion Channel Biophysics

Emerging Concepts in Ion Channel Biophysics

Poster Abstracts

8-POS

Board 8

Brownian Dynamics Study of Permeation and Selectivity of NaChBac and Its Mutants

Miraslau L. Barabash

, Dmitry G. Luchinsky

1,2

, William Gibby

, Carlo Guardiani

, Olena A.

Fedorenko

, Stephen K. Roberts

, Peter McClintock

Department of Physics, Lancaster University, LA1 4YB, Lancaster, Lancashire, United

Kingdom,

SGT Inc., Greenbelt 20770, MD, USA,

School of Engineering, University of

Warwick, CV4 7AL, Coventry, Warwickshire, United Kingdom,

Division of Biomedical and

Life Sciences, Lancaster University, LA1 4YG, Lancaster, Lancashire, United Kingdom.

We study the permeation and selectivity of NaChBac, a bacterial tetramer channel, using

Brownian dynamics (BD) simulations. The molecular structure of the selectivity filter (SF) has

been reconstructed in simulations recently [1], and thus our present study links this structure with

newly found experimental properties of the channel and its mutants [2].

We use BD to describe ionic motion through the SF, where the injection of ions is implemented

via the Grand Canonical Monte-Carlo scheme [3]. We apply the single-ion potentials of mean

force (PMFs), which are obtained from the molecular dynamics (MD) simulations [4, 5] thus

reflecting the structure of the channel protein. Ion-ion interactions are modelled via screened

Coulomb interactions. The model reproduces the electric current and spatial distribution of ions,

which are compared with experimental recordings of conduction and selectivity in the NaChBac

wild-type channel (LESWAS) and its mutants, LEDWAS, and LDDWAD [2]. The selectivity

between Na and K ions is found to arise from different PMFs seen by these ions, with a non-

monotonous current-concentration curve when the particle solutions contain both Na and K ions.

We believe the results can find application in physiology, as well as in artificial nanopores and

nanoscale fluid filters. The research was partially supported by the Engineering and Physical

Sciences Research Council UK (grant No. EP/M015831/1).

1. C. Guardiani et al., J. Chem. Theory Comput. 13 (3), pp 1389–1400 (2017)

2. O.A. Fedorenko, S.K. Roberts (in preparation)

3. W. Im et al., Biophys J. 79(2): 788–801 (2000)

4. M.A. Wilson, T.H. Nguyen, A. Pohorille, J. Chem .Phys. 141, 22D519 (2014)

5. C. Guardiani et al. (in preparation)