KOBRA: a fluctuating elastic rod model for slender biological macromolecules

Area of Science:

• Computational Biology
• Biophysics
• Molecular Modeling

Background:

• Elongated biomolecules, including alpha-helices and coiled-coils, play crucial roles in biological processes.
• Accurate dynamical simulations of these structures are essential for understanding their function.
• Existing methods may face limitations in simulating large-scale dynamics efficiently.

Purpose of the Study:

• To introduce KOBRA (KirchOff Biological Rod Algorithm), a novel algorithm and software package for simulating elongated biomolecules.
• To enable coarse-grained parameterization of complex biological structures with anisotropic and inhomogeneous properties.
• To validate KOBRA's performance against all-atom simulations and experimental data.

Main Methods:

• KOBRA represents biomolecules as coarsely-discretised Kirchoff rods with independent stretching, bending, and twisting capabilities.
• The algorithm incorporates non-inertial elements and thermal fluctuations for realistic simulations.
• Parameterization was performed using data from all-atom simulations of the Ndc80 protein complex.

Main Results:

• KOBRA simulations demonstrated high correlation in bend angle distributions and principal components with all-atom molecular dynamics and negative-stain EM data.
• The algorithm successfully captured the properties of a hinge region in the Ndc80 complex.
• KOBRA provides efficient access to timescales ranging from nanoseconds to seconds.

Conclusions:

• KOBRA is a fast and accurate tool for simulating the dynamics of elongated biomolecules.
• The algorithm's ability to reproduce experimental and all-atom simulation results highlights its potential for biological structure analysis.
• KOBRA offers a valuable coarse-grained approach for studying complex protein dynamics and structural features.