Parametrization of the Elastic Network Model Using High-Throughput Parallel Molecular Dynamics Simulations

Philipp S. Orekhov, Ilya V. Kirillov, Vladimir A. Fedorov, Ilya B. Kovalenko, Nikita B. Gudimchuk, Artem A. Zhmurov

Abstract


Even when modern computational platforms and parallel techniques are used, conventional all-atom simulations are limited both in terms of reachable timescale and number of atoms in the biomolecular system of interest. On the other hand, coarse-grained models, which allow to overcome this limitation, rely on proper and rigorous parametrization of the underlying force field. Here, we present a novel iterative approach for parametrization of coarse-grained models based on direct comparison of equilibrium simulations at all-atom and coarse-grained resolutions. In order to assess the accuracy of our method, we have built and parametrized an elastic network model (ENM) of the tubulin protolament consisting of four monomers. For this system, our method shows good convergence and the parametrized ENM reproduces protein dynamics in a finer way when compared to ENMs parametrized using the conventional approach. The presented method can be extended to other coarse-grained models with a slight adjustment of the equations describing the iterative scheme.


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References


Abraham, M.J., Murtola, T., Schulz, R., Pall, S., Smith, J.C., Hess, B., Lindahl, E.: Gromacs: High performance molecular simulations through multilevel parallelism from laptops to supercomputers. SoftwareX 1, 19–25 (2015), DOI: 10.1016/j.softx.2015.06.001

Hills, R.D., Brooks, C.L.: Insights from coarse-grained Go models for protein folding and dynamics. International journal of molecular sciences 10(3), 889–905 (2009), DOI: 10.3390/ijms10030889

Hyeon, C., Onuchic, J.N.: Mechanical control of the directional stepping dynamics of the kinesin motor. Proc. Natl. Acad. Sci. USA 104(44), 17382–17387 (2007), DOI: 10.1073/pnas.0708828104

Lyman, E., Pfaendtner, J., Voth, G.A.: Systematic multiscale parameterization of heterogeneous elastic network models of proteins. Biophysical journal 95(9), 4183–4192 (2008), DOI: 10.1529/biophysj.108.139733

Nogales, E.: Structural insights into microtubule function. Annual review of biochemistry 69(1), 277–302 (2000), DOI: 10.1146/annurev.biochem.69.1.277




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