Open AccessTubulin's response to external electric fields by molecular dynamics simulations
Author(s) -
Joshua J. Timmons,
Jordane Preto,
Jack A. Tuszyński,
Eric T. Wong
Publication year - 2018
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0202141
Subject(s) - electric field , tubulin , microtubule , molecular dynamics , dimer , biophysics , depolymerization , curvature , physics , elongation , instability , chemistry , biology , materials science , nuclear magnetic resonance , mechanics , microbiology and biotechnology , quantum mechanics , mathematics , geometry , organic chemistry , ultimate tensile strength , metallurgy
Tubulin heterodimers are the building blocks of microtubules and disruption of their dynamics is exploited in the treatment of cancer. Electric fields at certain frequencies and magnitudes are believed to do the same. Here, the tubulin dimer’s response to external electric fields was determined by atomistic simulation. External fields from 50 to 750 kV/cm, applied for 10 ns, caused significant conformational rearrangements that were dependent upon the field’s directionality. Charged and flexible regions, including the α:H1-B2 loop, β:M-loop, and C-termini, were susceptible. Closer inspection of the α:H1-B2 loop in lower strength fields revealed that these effects were consistent and proportional to field strength, and the findings indicate that external electric fields modulate the stability of microtubules through conformational changes to key loops involved in lateral contacts. We also find evidence that tubulin’s curvature and elongation are affected, and external electric fields may bias tubulin towards depolymerization.