Molecular dynamics simulation of the nanosecond pulsed electric field effect on kinesin nanomotor

Abstract

Kinesin is a biological molecular nanomotor which converts chemical energy into mechanical work. To fulfill various nanotechnological tasks in engineered environments, the function of biological molecular motors can be altered by artificial chemical modifications. The drawback of this approach is the necessity of designing and creating a new motor construct for every new task. We propose that intense nanosecond-scale pulsed electric field could modify the function of nanomotors. To explore this hypothesis, we performed molecular dynamics simulation of a kinesin motor domain docked on a subunit of its microtubule track - a single tubulin heterodimer. In the simulation, we exposed the kinesin motor domain to intense (100 MV/m) electric field up to 30 ns. We found that both the magnitude and angle of the kinesin dipole moment are affected. Furthermore, we found that the electric field affects contact surface area between kinesin and tubulin, the structure and dynamics of the functionally important kinesin segments, including microtubule binding motifs as well as nucleotide hydrolysis site which power the nanomotor. These findings indicate that external intense nanosecond-scale electric field could alter kinesin behavior. Our results contribute to developing novel electromagnetic methods for modulating the function of biomolecular matter at the nanoscale.

Figure 1

Nanomotor system analyzed in our molecular dynamics simulations: (a,b) kinesin motor domain docked on a tubulin heterodimer - subunit of the microtubule track. (b) the full all-atom molecular model used in simulations with water molecules and ions: tubulin heterodimer with kinesin motor domain (cyan), adenosine diphosphate (red), potassium ions K⁺ (blue) and chloride ions Cl⁻ (green) as dots. (c) close-up on kinesin motor domain on α, β-tubulin heterodimer: the α carbons in a whole tubulin except the red segments are restrained from motion to simulate the rigidity and mass of the whole microtubule. Important kinesin segments are color coded: nucleotide binding pocket containing P-loop (blue), switch I (red), switch II (dark green), and microtubule-binding motifs: loop L7 (purple), loop L8 (brown), loop L11 (yellow), α4 helix (light green), loop L12 (pink), α5 helix (cyan), and α6 helix (orange).

Figure 2

Plot of kinesin dipole moment dynamics, for five different electric field conditions: no electric field applied (black), 100 MV/m X direction (red); −X direction (magenta), Y (blue), −Y (cyan). The electric field is applied throughout the whole duration of the simulation. The thick line represents the average value and the shaded error bar depicts standard deviation (from N = 3 simulation replicates). (a,b) Display dipole moment (DM) magnitude for the whole duration of the simulation and for the first 1 ns, respectively, (c,d) display the differences of the average (across three simulation repetitions) DM magnitude values at individual field directions compared to no field condition. (e,f) Display dipole moment azimuth for the whole duration of the simulation and for the first 1 ns, respectively, (g,h) display the differences of the average values at individual field directions compared to no field condition. Images of kinesin bound to tubulin (i–p) from the end of the simulation, the kinesin dipole moment is depicted by the black arrow and the electric field vector E by the arrow color coded consistently with the data lines color.

Figure 3

Displacement analysis of kinesin C_α atoms for 100 MV/m electric field from the last 5 ns of the simulation for the field vector in the direction (a) X, (b) −X, (c) Y, (−Y). For each direction, we show the difference of x (X and −X field direction) or y (Y and −Y field direction) component of the C_α atom coordinate between field and no-field condition. Mean (thick line) and standard deviation (shaded error-bar envelope) is calculated from N = 750 frames (last 5 ns (250 frames), N = 3 simulations at each field direction). Important kinesin segments are highlighted by grey bars: nucleotide binding pocket containing P-loop (P), switch I (S I), switch II (S II), and MT-binding motifs loop L7, loop L8, loop L11, α4 helix, loop L12, α5 helix, and α6 helix. α-helices and β-sheets are denoted by grey and black horizontal bars on the top, respectively. Kinesin molecular model shows color-coded displacement (range from −3 to +3 Å) mapped on the protein secondary structure.

Figure 4

Root mean square fluctuations (RMSF) of C_α atoms for 100 MV/m electric field from 10 to 30 ns: (a) no field (black), X (red), −X (magenta), Y (blue), −Y (cyan) direction of the field vector. Functionally important kinesin segments are highlighted by grey vertical bars: nucleotide binding pocket containing P-loop (P), switch I (S I), switch II (S II) and microtubule-binding motifs loop L7, loop L8, loop L11, α4 helix, loop L12, α5 helix, and α6 helix. (b–e) RMSF of amplitude mapped on the kinesin structure for no field applied, four different viewing angles.

Figure 5

Contact surface area between kinesin and tubulin. Average (standard deviation) for each 5 ns long time interval is from N = 750 data points (250 data points from three MD run replicates). The graph displays averages for each 5 ns internal, the connecting line is plotted to guide reader’s eye. The color coding is consistent with earlier figures: black (no field), red (X EF direction), magenta (−X EF direction), blue (Y EF direction), and cyan (−Y EF direction).