Computing the Rotational Diffusion of Biomolecules via Molecular Dynamics Simulation and Quaternion Orientations.
Rotational diffusion (Drot) is a fundamental property of biomolecules that contains information about molecular dimensions and solute-solvent interactions. While ab initio Drotprediction can be achieved by explicit all-atom molecular dynamics simulations, this is hindered by both computational expense and limitations in water models. We propose coarse-grained force fields as a complementary solution, and show that the MARTINI force field with elastic networks is sufficient to compute Drotin >10 proteins spanning 5-157 kDa. We also adopt a quaternion-based approach that computes Drotorientation directly from autocorrelations of best-fit rotations as used in, e.g., RMSD algorithms. Over 2 μs trajectories, isotropic MARTINI+EN tumbling replicates experimental values to within 10-20%, with convergence analyses suggesting a minimum sampling of >50 × τtheorto achieve sufficient precision. Transient fluctuations in anisotropic tumbling cause decreased precision in predictions of axisymmetric anisotropy and rhombicity, the latter of which cannot be precisely evaluated within 2000 × τtheorfor GB3. Thus, we encourage reporting of axial decompositions Dx, Dy, Dzto ease comparability between experiment and simulation. Where protein disorder is absent, we observe close replication of MARTINI+EN Drotorientations versus CHARMM22*/TIP3p and experimental data. This work anticipates the ab initio prediction of NMR-relaxation by combining coarse-grained global motions with all-atom local motions.
Université de Lyon, CNRS, Université Claude Bernard Lyon1, Ens de Lyon, Institut des Sciences Analytiques , UMR 5280, 5 rue de la Doua, F-69100 Villeurbanne, France.
Po-Chia
0000-0003-2272-2082
PC
Chen
Université de Lyon, CNRS, Université Claude Bernard Lyon1, Ens de Lyon, Institut des Sciences Analytiques , UMR 5280, 5 rue de la Doua, F-69100 Villeurbanne, France.
Maggy
M
Hologne
Université de Lyon, CNRS, Université Claude Bernard Lyon1, Ens de Lyon, Institut des Sciences Analytiques , UMR 5280, 5 rue de la Doua, F-69100 Villeurbanne, France.
Olivier
O
Walker