Example 10: Cleaved, Asymmetric HIV-1 AE2 Env Ectodomain Trimer¶

PDB ID 8fae is a structure of the cleaved, asymmetric HIV-1 AE2 Env ectodomain trimer. Like Example 9: Cleaved, Asymmetric HIV-1 AD8 Env Ectodomain Trimer, this structure also contains bound instances of the entry inhibitor model BMS-806 (resname 83G).

The AE2 structure is slightly more compact than the AD8 structure, which is not suprising given that it was developed by introducing stabilizing mutations into the AD8 sequence. Viruses with both AD8 and AE2 Envs are capable of infecting human cells, and AE2 Env’s relatively higher stability makes it more resistant to neutralization by soluble CD4, CD4-mimetic compounds, and cold exposure.

# Author: Cameron F. Abrams, <cfa22@drexel.edu>
#
# pestifer input script
# 
# Simple build of solvated HIV-1 Env trimer 8fae
#
# Notes:
#   - Missing protein is built-in
#   - Drug molecule (resname 83G) is included (previously parameterized using cgenff)
#   - mmCIF input file requires careful attention to chainIDs and
#     residue numbers
#   - A five-phase NPT equilibration is used to settle the density
#   - A production tarball is generated: prod_8fae.tgz
#
title: HIV-1 Env Trimer 8fae
tasks:
  - fetch:
      sourceID: 8fae
      source_format: cif
  - psfgen:
      source:
        biological_assembly: 1
        remap_chainIDs:
          B: G
          D: H
          E: I
          A: B
          F: D
        sequence:
          glycans:
            declash:
              maxcycles: 500
  - validate:
      tests:
        - residue_test:
            name: 83G ligands are present
            selection: resname 83G
            measure: residue_count
            value: 3
  - md:
      ensemble: minimize
  - ligate:
      steer:
        nsteps: 4000
  - validate:
      tests:
        - connection_test:
            name: gp120 gap ligations
            selection: protein and chain G H I and resid 112 113
            connection_type: interresidue
            connection_count: 3
  - md:
      ensemble: minimize
  - md:
      cpu-override: True
      ensemble: NVT
  - solvate:
  - md:
      ensemble: minimize
  - md:
      ensemble: NVT
  - md:
      ensemble: NPT
      nsteps: 200
  - md:
      ensemble: NPT
      nsteps: 400
  - md:
      ensemble: NPT
      nsteps: 800
  - md:
      ensemble: NPT
      nsteps: 1600
  - md:
      ensemble: NPT
      nsteps: 13200
  - mdplot:
      timeseries:
        - density
      basename: solvated
      grid: True
  - terminate:
      basename: my_8fae
      artifacts: artifacts
      package:
        basename: prod_8fae
        namd:
          ensemble: NPT

Pipeline task summary¶
Step	Task	Details
1	`fetch`	PDB 8FAE
2	`psfgen`	standard build
3	`validate`	1 test(s)
4	`md`	minimize
5	`ligate`	ligate chain breaks (steered MD, 4,000 steps)
6	`validate`	1 test(s)
7	`md`	minimize → NVT (2,000 steps)
8	`solvate`	water box
9	`md`	minimize → NVT (2,000 steps) → NPT (16,200 steps, 5 phases)
10	`mdplot`	equilibration time-series plots → `mdplots/`
11	`terminate`	basename: `my_8fae`; package: `prod_8fae`

Reference¶

Asymmetric conformations of cleaved HIV-1 envelope glycoprotein trimers in styrene-maleic acid lipid nanoparticles. Wang, K., Zhang, S., Go, E.P., Ding, H., Wang, W.L., Nguyen, H.T., Kappes, J.C., Desaire, H., Sodroski, J., Mao, Y. Commun Biol 6: 535 DOI 10.1038/s42003-023-04916-w (2023)