Conduction and Gating Properties of the TRAAK Channel from Molecular Dynamics Simulations with Different Force Fields

• Published in: Journal of chemical information and modeling Vol. 60; no. 12; pp. 6532 - 6543
• Main Authors: Ocello, Riccardo, Furini, Simone, Lugli, Francesca, Recanatini, Maurizio, Domene, Carmen, Masetti, Matteo
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 28.12.2020
• Subjects: Accessibility; Computational Biochemistry; Ion channels; Molecular dynamics; Simulation
• ISSN: 1549-9596; 1549-960X; 1549-960X
• DOI: 10.1021/acs.jcim.0c01179

In recent years, the K2P family of potassium channels has been the subject of intense research activity. Owing to the complex function and regulation of this family of ion channels, it is common practice to complement experimental findings with the atomistic description provided by computational approaches such as molecular dynamics (MD) simulations, especially, in light of the unprecedented timescales accessible at present. However, despite recent substantial improvements, the accuracy of MD simulations is still undermined by the intrinsic limitations of force fields. Here, we systematically assessed the performance of the most popular force fields employed to study ion channels at timescales that are orders of magnitude greater than the ones accessible when these energy functions were first developed. Using 32 μs of trajectories, we investigated the dynamics of a member of the K2P ion channel family, the TRAAK channel, using two established force fields in simulations of biological systems: AMBER and CHARMM. We found that while results are comparable on the nanosecond timescales, significant inconsistencies arise at microsecond timescales.