# YASARA MACRO
# TOPIC:       5. Structure prediction
# TITLE:       Building a protein model
# REQUIRES:    Structure
# AUTHOR:      Elmar Krieger
# LICENSE:     GPL
# DESCRIPTION: This macro builds a protein model using a FASTA sequence of the target, and optionally template structures and alignments. AI-based ab initio structure predictions are made locally using ESMFold and OmegaFold (7 GB of disk space needed). If 'foldmethod' is set to 'All', AlphaFold predictions will also be used (75 GB of disk space needed).

# Parameter section - adjust as needed, but NOTE that some changes only take effect
# if you start an entirely new modeling job, not if you continue an existing one. 
# =================================================================================

# You can either set the target structure by clicking on Options > Macro > Set target,
# by providing it as command line argument (see docs at Essentials > The command line),
# or by uncommenting the line below and specifying it directly.
#MacroTarget '/home/myname/projects/proteinmodels/t0120'

# AI-based folding methods used to create templates, you can combine AlphaFold, ESMFold and
# OmegaFold with '+' in this order, use 'all' for all three.
foldmethod='ESMFold+OmegaFold'
# Uncomment below to use AlphaFold predictions from the AlphaFold database at EBI too (requires 75 GB disk space for the sequences)
# foldmethod='All'

# Number of PSI-BLAST iterations
# Set to '1' to search the template with a simple BLAST, not a PSSM-based PDB-BLAST
psiblasts=3

# Maximum PSI-BLAST Evalue allowed for templates
evalue=0.5 

# Maximum number of templates to use (if you provide fewer templates, the others will be picked by YASARA) 
templates=5

# Maximum number of ambiguous alignments to consider per template
alignments=5

# Maximum oligomerization state, build at most decameric models
oligostate=10

# Maximum number of unaligned loop residues to add to the termini
termextension=10

# Normally no change required below this point
# ============================================
RequireVersion 24.3.1

# Sanity checks
if MacroTarget==''
  RaiseError "This macro requires a target. Either edit the macro file or click Options > Macro > Set target to choose a target sequence"

Clear

# Do we have a target sequence? 
command1='pass'
seqfilename='(MacroTarget).fasta'
seq = FileSize (seqfilename) 
if seq
  # Yes, create a command to specify the sequence file
  command1='SequenceFile (seqfilename)'
  
# Do we have alignments?
alifilename='(MacroTarget)_align.fasta'
ali = FileSize (alifilename) 
if ali
  # Yes, use the alignments instead of the target sequence
  command1='AlignFile (alifilename)'
  
if !seq and !ali
  RaiseError 'Neither a sequence file (seqfilename), nor an alignment file (alifilename) was found, no model can be built'  
  
# Do we have templates?
command2='pass'
for i=001 to 999
  for ext in 'yob','pdb'
    tmpfilename='(MacroTarget)_t(i).(ext)'
    tmp = FileSize (tmpfilename)
    if tmp
      # Load template and name it T001.. 
      tmp = Load(ext) (tmpfilename)
      NameObj (tmp),T(i)
      # Create command to select all templates
      command2='TemplateObj all'
      # Template found, try next
      continue 2
  break

# Build the model
Experiment ProteinModeling
  # Specify either a target sequence or an alignment file
  (command1)
  # Select any templates that have been loaded
  (command2)
  # Use AI-based ab initio folding
  FoldMethod (foldmethod)
  # Set parameters defined at the beginning
  # Number of PSI-BLAST iterations
  PsiBLASTs (psiblasts)
  # The maximum PSI-BLAST Evalue (minimum can be set to avoid easy models)
  EValue Max=(evalue),Min=0
  # Maximum oligomerization state
  OligoState (oligostate)
  # Maximum number of templates to consider, and how many with the same sequence
  Templates (templates),SameSeq=1
  # Maximum number of ambiguous alignments to consider per template
  Alignments (alignments)
  # Maximum number of terminal loop residues
  TermExtension (termextension)
  # Speed of animations: fast/normal/slow
  Animation Normal
  # Number of samples to try per loop (see OptimizeLoop command)
  LoopSamples 50
  # Use structure-based profiles if available
  StructProfile try
  # The common start for result filenames
  ResultFile (MacroTarget)
  # Uncomment below if you do not want to access PDB_REDO
  # PDBREDO No
  # Uncomment below to select certain template residues for deletion, e.g. het-groups. See user manual at 'Selections'.
  # DelTemplateRes Hetgroup
  # Uncomment below to require certain template residues (e.g. co-factors), see user manual at 'Selections'.
  # ReqTemplateRes FAD FMN with distance<10 from HEM
  # Uncomment below to rank certain templates first (only affects templates found by YASARA)
  # TemplateList 2ZPY,2HE7,2I1K
  # Uncomment below to specify a list of excluded templates
  # TemplateExList 1CRN,5TIM,1AON
  # Uncomment below to add alignment anchors, see Recipes > Build a protein model > Useful hints
  # Equivalence Target=DHFGRER,Template=FDGFHGR
  # Uncomment below to keep the side-chains of selected conserved residues fixed, e.g. target residues 90 and 105
  # FixModelRes 90 105
  # Uncomment below to keep the side-chains of all conserved residues fixed (only useful if seqID near 100%).
  # FixModelRes conserved
  # Uncomment below to accept only templates that cover the selected target residues, e.g. residues 95 and 110
  # RequireRes 95 110
  # Uncomment below to skip loops that are longer than 9 residues (models will have gaps, no hybrid model built)
  # LoopLenMax 9
  # Uncomment below to build models with reduced accuracy as quickly as possible
  # Speed fast
  # Uncomment below to use your own secondary structure prediction
  # SecStrFile YourModel_secstr.ali
  # Uncomment below to save time by disabling the protein modeling report
  # Report no
Experiment On
Wait ExpEnd

# Exit YASARA if this macro was provided as command line argument in console mode and not included from another macro
if runWithMacro and ConsoleMode and !IndentationLevel
  Exit
# Show protein modeling report if present (can be disabled with Report no)
reported=FileSize (MacroTarget).html
if reported and !ConsoleMode
  ShowURL file://(MacroTarget).html