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An Automated Pipeline for HIV-1 Envelope Glycoprotein Sequence Design To Achieve Prefusion-Closed Trimers

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ADROITrimer

An Automated Pipeline for HIV-1 Envelope Glycoprotein Sequence Design To Achieve Prefusion-Closed Trimers

Installation

ADROITrimer has been successfully tested on Mac and Linux systems

Dependencies

  • MUSCLE alignment software (https://www.drive5.com/muscle/). Please download and install.
  • The R Project for Statistical Computing (https://www.r-project.org/). Please download and install
  • R library bio3d: In command line type
    • R
    • In R console type: install.packages("bio3d")
    • Exit R console with CRTL-D

Run

ADROITrimer can be run in the command line

Dependencies

3 files are required to be placed in current work directory (please download them from this repository from the required_files sub-directory)

  1. HIV1_FLT_2016_env_PRO_cleanLastCol_final.fasta
  2. 5fyl_trimer.pdb
  3. 5fyl_trimer.rsa

3 input arguments are necessary to run the ADROITrimer

  1. HIV-1 Env target sequence (sequence you would like to be optimized) in FASTA format
  2. Clade/Subtype of target sequence (Clade can be for instance determined using RIP from LANL: https://www.hiv.lanl.gov/content/sequence/RIP/RIP.html)
  3. Path to installed MUCLE software (e.g. "/usr/local/bin/muscle")

Execute in the command line

R --no-save < ADROITrimer1.0-3.R target.fasta A /usr/bin/muscle

Result

Multiple analysis and output files will be provided. The critical DS-SOSIP-RnS stabilized sequences are provided in FASTA format. In particular,

  1. With N- and C-terminal tags (N-terminal - Prolactin leader sequence, C-terminal - D7324-tag): output_xxx_DS-SOSIP-RnS_NtCt-tags.fasta (with xxx being a numeric value - time stamp)
  2. Without N- and C-terminal tags: output_xxx_DS-SOSIP-RnS.fasta (with xxx being a numeric value - time stamp) You would have to add signal peptide and any desired C-terminal tag.

Example/Test

Clade A Strain BG505 testing sequence (please find BG505.W6M.C2.fasta example sequence in example sub-directory)

R --no-save < ADROITrimer1.0-1.R BG505.W6M.C2.fasta A /usr/bin/muscle

Contact

Reda Rawi: reda.rawi@nih.gov

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An Automated Pipeline for HIV-1 Envelope Glycoprotein Sequence Design To Achieve Prefusion-Closed Trimers

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