Higher H-bonds stabilities from 72 SOD1 mutants associated with ALS

Published: 06-10-2020| Version 1 | DOI: 10.17632/vfpt7dzvht.1
Contributor:
Nikolay Alemasov

Description

As a characteristic of hydrogen bonds, the stability of hydrogen bonds was calculated as the number of conformations in which the bond was present, referred to the total number of conformations. A table of the stabilities of all hydrogen bonds found in the studied SOD1 mutants was constructed. A threshold was applied for the calculated stabilities such that a hydrogen bond must have stability at least 0.8 in any mutant.

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Steps to reproduce

For simulation, 72 mutants of the SOD1 protein were selected from Wang et al., 2008. The initial structure is taken from PDBID: 2V0A. The mutant structures were modeled using the PDBfixer program (https://github.com/openmm/pdbfixer). Simulating the dynamics of mutant SOD1 was performed using the OpenMM platform (Eastman et al., 2017). Below is the simulation protocol: 1. Temperature: 298 K, 2. Pressure: 1 bar, 3. Collision rate: 1 ps^{-1}, 4. Integration step: 5 fs, 5. Tolerance constraints (constraint tolerance): 1*10^{-5}, 6. Method for calculating non-binding interactions: PME, 7. Cutoff radius of nonbonding interactions: 1 nm, 8. Restrictions were set for all bonds (AllBonds, both for lengths and angles), 9. The model of hard water was used (restrictions on connections are set: both for lengths and for angles), 10. The mass of hydrogen atoms was taken equal to 4 amu (the HMR approach was used), 11. Copper and zinc ions were included in the protein structure with the addition of harmonic potentials (HarmonicRestraintBondForce) between the ion and the nearest atoms of the amino acid residues coordinating the ion, with hardness constants 0.2 kcal/mol/A^2; potentials were added (the position of the remainder in the sequence and the name of the atom in the remainder are indicated): 11.1 between the zinc ion and the following atoms: 63@ND1, 71@ND1, 80@ND1, 83@OD1, 83@OD2; 11.2 between the copper ion and the following atoms: 46@ND1, 48@NE2, 63@NE2, 120@NE2, 118@CG1, 118@CG2; 12. Model of water molecules: tip3p, 13. Size of the solvent layer around the molecule: 0.6 nm, 14. Concentration of Na$^+$ and Cl$^-$ ions: 0.15 M, 15. We used a Langevin integrator, a Monte Carlo barostat, 16. Minimization: 200 steps by gradient descent, 17. Equilibration: 50 ps, 18. MD simulation for statistics collection: 10 ns, 19. Working MD start using a dual aMD integrator (DualAMDIntegrator): 10 ns. MDTraj (McGibbon et al., 2015) library was used to analyze MD trajectories. The detection of hydrogen bonds in the MD trajectory was carried out using MDTraj using the Wernet-Nilsson method. As a characteristic of hydrogen bonds, the stability of hydrogen bonds was calculated as the number of conformations in which the bond was present, referred to the total number of conformations. A table of the stabilities of all hydrogen bonds found in the studied SOD1 mutants was constructed.