Continuum mechanical parameterisation of cytoplasmic dynein from atomistic simulation

• Published in: Methods (San Diego, Calif.) Vol. 185; pp. 39 - 48
• Main Authors: Hanson, Benjamin S., Iida, Shinji, Read, Daniel J., Harlen, Oliver G., Kurisu, Genji, Nakamura, Haruki, Harris, Sarah A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2021
• Subjects: algorithms; Dynein; dynein ATPase; eukaryotic cells; finite element analysis; Fluctuating finite element analysis; Hierarchical biomechanics; mechanics; Molecular dynamics; Multiscale simulation; physiological transport; Principal component analysis; proteins; viscoelasticity; Hierarchical biomechanics; Fluctuating finite element analysis; MT; Molecular dynamics; Multiscale simulation; ADP; MTBD; PCA; MD; Dynein; FFEA; ATP; Principal component analysis
• ISSN: 1046-2023; 1095-9130; 1095-9130
• DOI: 10.1016/j.ymeth.2020.01.021

•MD simulations of cytoplasmic dynein show stalk angular fluctuations are significant.•The measured dynamics can be well represented at a coarse-grained level using FFEA.•Continuum parameterisation captures the higher flexibility of the ATP-bound motor. Cytoplasmic dynein is responsible for intra-cellular transport in eukaryotic cells. Using Fluctuating Finite Element Analysis (FFEA), a novel algorithm that represents proteins as continuum viscoelastic solids subject to thermal noise, we are building computational tools to study the mechanics of these molecular machines. Here we present a methodology for obtaining the material parameters required to represent the flexibility of cytoplasmic dynein within FFEA from atomistic molecular dynamics (MD) simulations, and show that this continuum representation is sufficient to capture the principal dynamic properties of the motor.