Computational protocol: A Mechanistic Understanding of Allosteric Immune Escape Pathways in the HIV-1 Envelope Glycoprotein

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Protocol publication

[…] The missing regions of the structures for the YU2, HXB2, and CAP210 sequences (PDB accession numbers 1G9M , 1RZK , and 3LQA ) lacking the V1–V3 loops were modeled using the MODELLER program . The core of gp120 was similar in all these structures. It should be noted that 3LQA is the only high-resolution structure of a clade C gp120 sequence, while multiple clade B gp120 structures exist. Multiple templates were used because it has been shown that this creates a high-quality homology model. During modeling, disulfide constraints were added for the conserved cysteines present in all gp120 sequences. All sequence alignments used for modeling templates were based on sequences in the HIV-1 database ( [...] The starting conformations for the long timescale all-atom MD simulations were modeled using MODELLER as described above. The protein was solvated in TIP3P water molecules and neutralized in 150 mM NaCl salt. The MD simulations of the solvated proteins were performed using NAMD2 with the CHARMM27 force field . The protein was initially minimized and then heated to 298K with constraints added during these steps similar to the protocol in . All simulations were performed with periodic boundary conditions using the NPT ensemble with pressure set to 1 atmosphere and temperature set to 298K. The pressure and temperature were maintained using the Langevin piston and the Langevin theromostat respectively. Electrostatics were calculated with the particle mesh Ewald method . The van der Waals interactions were calculated using a switching distance of 10 Angstroms and a cutoff of 12 Angstroms. All the production runs were performed with 2 fs time step using the RATTLE and SETTLE algorithms. The proteins were equilibrated for 10 ns, and the initial burst in RMSD converged within this period. The YU2, HXB2, and CAP210 simulations were performed for a further 600 ns each. The number of atoms in each system was approximately 50,000 atoms. The coordinates were saved once every 1 ps in each simulation. […]

Pipeline specifications

Application Protein structure analysis
Organisms Human immunodeficiency virus 1
Diseases Genetic Diseases, Inborn