An in silico tool to optimize protein interaction energies

iSAPIENS has been successfully tested on Linux systems

• Install R and required libraries:
  • R
  • R libraries
    • Within R execute the following command: install.packages( "bio3d" )
    • • Within R execute the following command: install.packages( "doParallel" )
    • Download R's Interpol package (https://cran.r-project.org/src/contrib/Archive/Interpol/Interpol_1.3.1.tar.gz) and install manually: Within R terminal execute: install.packages("Interpol_1.3.1.tar.gz", source = TRUE, repos = NULL )
  • FoldX (https://foldxsuite.crg.eu/)
  • VMD (https://www.ks.uiuc.edu/Research/vmd/)
    • We used VMD version "VMD for LINUXAMD64, version 1.9.3"
  • NAMD (https://www.ks.uiuc.edu/Research/namd/)
    • We used NAMD version "NAMD_2.13_Linux-x86_64-multicore"
    • Download required NAMD CHARMM parameter and topology files; in particular
      • top_all36_prot.rtf
      • top_all36_carb.rtf
      • toppar_water_ions_namd.str
      • par_all36_prot_cu_patch.prm
      • par_all36_carb.prm
      • toppar_water_ions_namd.str
  • YASARA (https://www.yasara.org/)

iSAPIENS can be run in the command line

• Antigen - Antibody complex
  • Antigen (chain A)
  • Antibody (chain H and chain L)
• Number of CPUs
• Path to FoldX executable
• Path to VMD executable
• Path to NAMD executable
• NAMD topology files separated by "___"
• NAMD parameter files separated by "___"
• Path to YASARA executable
• Path to YASARA homology modeling script (attached here: YASARA_EM.mcr)
• Cutoff (We used 12Å)
• Option (1: Interface, 2: Stability, 3: Interface + Stability)
• Interface Chain(s) 1: We used "A"
• Interface Chain(s) 2: We used "H_L"
• Stability Chain(s) 1: We used "H_L"
• Stability Chain(s) 2: We used "H_L"

Need to generate mutation file using FoldX syntax (see attached example: "individual_list.txt")

• Option 1: Antigen-antibody interface protein interaction energies
  • R --no-save < iSAPIENS_v1.0.0.R File.pdb nCPU PathToFoldx PathToVMD PathToNAMD top_all36_prot.rtf___top_all36_carb.rtf___toppar_water_ions_namd.str par_all36_prot_cu_patch.prm___par_all36_carb.prm___toppar_water_ions_namd.str PathToYASARA YASARA_EM.mcr 12 1 A H_L
• Option 2: Antibody stability and inter-chain interaction energies
  • R --no-save < iSAPIENS_v1.0.0.R File.pdb nCPU PathToFoldx PathToVMD PathToNAMD top_all36_prot.rtf___top_all36_carb.rtf___toppar_water_ions_namd.str par_all36_prot_cu_patch.prm___par_all36_carb.prm___toppar_water_ions_namd.str PathToYASARA YASARA_EM.mcr 12 2 H_L H_L
• Option 3: Option 1 and 2
  • R --no-save < iSAPIENS_v1.0.0.R File.pdb nCPU PathToFoldx PathToVMD PathToNAMD top_all36_prot.rtf___top_all36_carb.rtf___toppar_water_ions_namd.str par_all36_prot_cu_patch.prm___par_all36_carb.prm___toppar_water_ions_namd.str PathToYASARA YASARA_EM.mcr 12 3 A H_L H_L H_L

Examples (use files provided in repository):

• R --no-save < iSAPIENS_v1.0.0.R m42_HH28K_13_renum.pdb 48 PathToFoldx PathToVMD PathToNAMD top_all36_prot.rtf___top_all36_carb.rtf___toppar_water_ions_namd.str par_all36_prot_cu_patch.prm___par_all36_carb.prm___toppar_water_ions_namd.str PathToYASARA YASARA_EM.mcr 12 1 A H_L
• R --no-save < iSAPIENS_v1.0.0.R m42_HH28K_13_renum.pdb 48 PathToFoldx PathToVMD PathToNAMD top_all36_prot.rtf___top_all36_carb.rtf___toppar_water_ions_namd.str par_all36_prot_cu_patch.prm___par_all36_carb.prm___toppar_water_ions_namd.str PathToYASARA YASARA_EM.mcr 12 2 H_L H_L
• R --no-save < iSAPIENS_v1.0.0.R m42_HH28K_13_renum.pdb 48 PathToFoldx PathToVMD PathToNAMD top_all36_prot.rtf___top_all36_carb.rtf___toppar_water_ions_namd.str par_all36_prot_cu_patch.prm___par_all36_carb.prm___toppar_water_ions_namd.str PathToYASARA YASARA_EM.mcr 12 3 A H_L H_L H_L

Mateo Reveiz et al.; In Silico Improvement of Highly Protective Anti-Malarial Antibodies, bioRxiv, 2022, https://www.biorxiv.org/content/10.1101/2022.04.08.487687v1

Reda Rawi: reda.rawi@nih.gov