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Keep It Flexible: Driving Macromolecular Rotary Motions in Atomistic Simulations with GROMACS.

Kutzner C, Czub J, Grubmüller H - J Chem Theory Comput (2011)

Bottom Line: In particular, we introduce a "flexible axis" technique that allows realistic flexible adaptions of both the rotary subunit as well as the local rotation axis during the simulation.A variety of useful rotation potentials were implemented for the GROMACS 4.5 MD package.Application to the molecular motor F(1)-ATP synthase demonstrates the advantages of the flexible axis approach over the established fixed axis rotation technique.

View Article: PubMed Central - PubMed

Affiliation: Department of Theoretical and Computational Biophysics, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany.

ABSTRACT
We describe a versatile method to enforce the rotation of subsets of atoms, e.g., a protein subunit, in molecular dynamics (MD) simulations. In particular, we introduce a "flexible axis" technique that allows realistic flexible adaptions of both the rotary subunit as well as the local rotation axis during the simulation. A variety of useful rotation potentials were implemented for the GROMACS 4.5 MD package. Application to the molecular motor F(1)-ATP synthase demonstrates the advantages of the flexible axis approach over the established fixed axis rotation technique.

No MeSH data available.


RMSD of the γ subunit backbone atoms with respect to the X-ray structure as a function of time for the F1 motor driven to rotate in the synthesis direction using the potentials Viso (A), Vflex (B), and Vflex2 (C) with spring constants k of 100−800 kJ/(mol·nm2).
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fig7: RMSD of the γ subunit backbone atoms with respect to the X-ray structure as a function of time for the F1 motor driven to rotate in the synthesis direction using the potentials Viso (A), Vflex (B), and Vflex2 (C) with spring constants k of 100−800 kJ/(mol·nm2).

Mentions: For a quantitative comparison of the γ subunit internal deformation, Figure 7 shows the time evolution of the RMSD of the γ backbone atoms from their initial configuration. Relatively small RMSD variations are observed for the fixed method, confirming nearly rigid-body like rotation. In contrast, both flexible axis methods allow for structural rearrangements particularly for small k values. A secondary structure analysis shows that for the F1-ATPase flexibly rotating at 0.021°/ps the force constant k should be 200 kJ/(mol·nm2) or larger to preserve the rotor coiled-coil conformation of the crystal structure (Figure 4). For any of the rotation potentials, the force constant will depend on the studied system and on the rotation rate. Generally, higher rotation rates will require larger force constants that stabilize the rotation group with the help of a stronger coupling to its reference. Yet, the decrease in conformational freedom with increasing k (Figure 7) shows that when using the flexible axis approach one can optimize the tradeoff between structural flexibility and mechanical resistance of the rotary subunit. Note that the 120° rotations, in principle, cannot perfectly reproduce the starting configuration of the F1-ATPase, as in our simulations the rotor motion is not accompanied by occupancy changes of the active sites.


Keep It Flexible: Driving Macromolecular Rotary Motions in Atomistic Simulations with GROMACS.

Kutzner C, Czub J, Grubmüller H - J Chem Theory Comput (2011)

RMSD of the γ subunit backbone atoms with respect to the X-ray structure as a function of time for the F1 motor driven to rotate in the synthesis direction using the potentials Viso (A), Vflex (B), and Vflex2 (C) with spring constants k of 100−800 kJ/(mol·nm2).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3091370&req=5

fig7: RMSD of the γ subunit backbone atoms with respect to the X-ray structure as a function of time for the F1 motor driven to rotate in the synthesis direction using the potentials Viso (A), Vflex (B), and Vflex2 (C) with spring constants k of 100−800 kJ/(mol·nm2).
Mentions: For a quantitative comparison of the γ subunit internal deformation, Figure 7 shows the time evolution of the RMSD of the γ backbone atoms from their initial configuration. Relatively small RMSD variations are observed for the fixed method, confirming nearly rigid-body like rotation. In contrast, both flexible axis methods allow for structural rearrangements particularly for small k values. A secondary structure analysis shows that for the F1-ATPase flexibly rotating at 0.021°/ps the force constant k should be 200 kJ/(mol·nm2) or larger to preserve the rotor coiled-coil conformation of the crystal structure (Figure 4). For any of the rotation potentials, the force constant will depend on the studied system and on the rotation rate. Generally, higher rotation rates will require larger force constants that stabilize the rotation group with the help of a stronger coupling to its reference. Yet, the decrease in conformational freedom with increasing k (Figure 7) shows that when using the flexible axis approach one can optimize the tradeoff between structural flexibility and mechanical resistance of the rotary subunit. Note that the 120° rotations, in principle, cannot perfectly reproduce the starting configuration of the F1-ATPase, as in our simulations the rotor motion is not accompanied by occupancy changes of the active sites.

Bottom Line: In particular, we introduce a "flexible axis" technique that allows realistic flexible adaptions of both the rotary subunit as well as the local rotation axis during the simulation.A variety of useful rotation potentials were implemented for the GROMACS 4.5 MD package.Application to the molecular motor F(1)-ATP synthase demonstrates the advantages of the flexible axis approach over the established fixed axis rotation technique.

View Article: PubMed Central - PubMed

Affiliation: Department of Theoretical and Computational Biophysics, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany.

ABSTRACT
We describe a versatile method to enforce the rotation of subsets of atoms, e.g., a protein subunit, in molecular dynamics (MD) simulations. In particular, we introduce a "flexible axis" technique that allows realistic flexible adaptions of both the rotary subunit as well as the local rotation axis during the simulation. A variety of useful rotation potentials were implemented for the GROMACS 4.5 MD package. Application to the molecular motor F(1)-ATP synthase demonstrates the advantages of the flexible axis approach over the established fixed axis rotation technique.

No MeSH data available.