DOI: 10.5281/zenodo.4483108
title: All-atom Molecular Dynamics Simulations of Filamin-A Actin-binding Domain, Immunoglobulin-like Domains 3, 4, 5, 21 and 24 to Investagate the Impact of Known Missense Mutations Associated with Periventricular Nodular Heterotopia in the Liveborn Males

description: Data includes all of the wild-type and mutant trajectories of classical all-atom molecular dynamics (MD) simulations of Filamin-A (FLNa, the product of <em>FLNA</em> gene located on chromosome X). Wild-type proteins are from the PDB structures with IDs: 4M9P, 3HOP, 3CNK and 2BRQ. The mutations, including R484Q that we discovered in a Turkish family, were formerly found in the liveborn males with <em>FLNA</em>-associated periventricular nodular heterotopia (PNH), who survived with the only copy of mutated <em>FLNA</em>. To understand how these mutations lead to the PNH and simultaneously allow their survival, we performed these MD simulations for the wild-type and mutant systems. Systems were prepared in Visual Molecular Dynamics (VMD 1.9.3) by placing them in a TIP3P water box with approximately 20 Å thickness from the protein surface and neutralizing the system by adding counter ions in the form of NaCl. Of note, only protein parts were kept for the submission to reduce the size of files. Nanoscale Molecular Dynamics (NAMD 2.13-CUDA) was used to perform MD simulations with CHARMM36m force field. For pressure and temperature controls, Nosé-Hoover Langevin barostat and Langevin thermostat were used. ShakeH algorithm of NAMD was applied for water molecule constraints. 12 Å cut-off distance was used for van der Waals interactions. Switching function starts at 10 Å and reaches zero at 14 Å. Integration time-step was 2 fs. To compute the long-range Coulomb interactions, the particle-mash Ewald method was used. After a 10000-step minimization with conjugate gradient algorithm and an equilibration for 1 ns at 298 K under NVT ensemble, production simulations were run twice along 100 ns by using different random seeds to assign the velocities from Boltzmann distribution (total simulation time for each system was 200 ns, which are given as 100 ns repeat 1, and 100 ns repeat 2). Only the production simulations were supplied in this dataset. Example configuration files are also available for 4m9p wild-type, and other trajectories were also obtained by the same configuration.
description: Further information can be requested from http://www.sezermanlab.org/, or umut.gerlevik@gmail.com.
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