Computational protocol: Computational Exploration for Lead Compounds That Can Reverse the Nuclear Morphology in Progeria

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Protocol publication

[…] To further affirm the potentiality of the selected compounds and to evaluate the dynamic behaviour of the prospective drug molecules in the binding site pocket, they were subjected to MD simulations along with the reference compounds using GROMACS 4.5.7, employing CHARMm27 force field []. MD simulations were executed to examine the binding stability of the identified lead compounds in comparison with the reference compound. Ligand topologies were generated using SwissParam []. Corresponding counter ions were added to neutralize the solvated TIP3P water model present in the dodecahedron box. Unwanted contacts from the initial structure were dislodged by performing the energy minimization, adapting the steepest descent algorithm which was followed by the NVT and NPT equilibration steps. During this process, the solvent molecules along with the counter ions were allowed to move restraining the protein backbone. Both the processes were executed for 100 ps at 300 K and a pressure of 1 bar, respectively. Parrinello-Rahman barostat was employed to maintain the pressure of the system []. The geometry of the water molecules and the bonds involving hydrogen atoms were constrained employing the SETTLE [] and LINCS [], respectively. Particle Mesh Ewald (PME) [] was used to calculate long-range electrostatic interactions. A cut-off distance of 12 Å was attributed for Coulombic and van der Waals interactions. The equilibrated structures were then subjected to production run which was conducted for 20 ns and the results were evaluated using VMD [] and DS. […]

Pipeline specifications

Software tools GROMACS, SwissParam, P-LINCS, VMD
Applications Drug design, Protein structure analysis
Diseases Neural Tube Defects, Genetic Diseases, Inborn