Recipe: Helix Rebuild 5.1

created by spvincent

Profile

• Name: Helix Rebuild 5.1
• ID: 100725
• Shared with: Public
• Parent: HR 5.1
• Children:
  • Helix Rebuild 5.1 No Mutate
  • Multiwalker for locked ones v0.7
• Created on: February 24, 2015 at 02:24 AM UTC
• Updated on: February 24, 2015 at 02:24 AM UTC
• Description:

  see first comment

Code

-- Globals

original_secondary_structure = {}
fixed_residues = {}

helix_starts = {}
helix_ends  = {}
use_helix = {}
n_helices = 0

n_residues = 0

loop_spacer = 4

n_rebuilds = 6

score_type = 1
original_slow_filters_setting = 0
best_score = 0

mutate_not_shake = false
test_for_credit = false

-- Quicksave slots

kOriginalStructureOrNewBest = 1	  -- the starting structure, or any subsequent improvement, will be stored in this quicksave slot
kBestPostRebuild_a = 2
kBestPostRebuild_b = 3
kBestPostRebuild_a_post_wiggle = 4
kTemp = 5
kBestWithSpacers = 6

kWiggleDuration = 12

inner_cylinder = {}
outer_cylinder = {}

inner_cylinder_radius = 12
outer_cylinder_radius = 16

pw_threshold_value = 100

function r3 ( i )

-- printing convenience

   return i - i % 0.001

end

function GetScore ()

    if ( score_type == 1 ) then

        score = current.GetEnergyScore () 

    elseif ( score_type == 2 ) then

        behavior.SetSlowFiltersDisabled ( false )
        score = current.GetScore () 
        behavior.SetSlowFiltersDisabled ( true )

    end

    return score

end

function DoesPuzzleHaveSlowFilters ()

    init_setting = behavior.GetSlowFiltersDisabled ()
 
    if ( init_setting == false ) then
       score_without_sf = current.GetScore () 
       behavior.SetSlowFiltersDisabled ( true )
       score_with_sf = current.GetScore () 
     else
       score_with_sf = current.GetScore () 
       behavior.SetSlowFiltersDisabled ( false )
       score_without_sf = current.GetScore () 
    end

    behavior.SetSlowFiltersDisabled ( init_setting )
 
    if ( math.abs ( score_without_sf - score_with_sf ) >1e-3 ) then
        return true
      else
        return false
    end

end


function IsPuzzleMutable ()

    for i = 1 , n_residues do
       if ( structure.IsMutable ( i ) ) then
           return true
       end
    end

    return false

end


function GetHelices ()

    within_helix = false
  
    for i = 1, n_residues do

        if ( structure.GetSecondaryStructure ( i ) == "H" ) then
    
           if ( within_helix == false ) then

                -- start of a new helix

                within_helix = true

                n_helices = n_helices + 1
                helix_starts [ n_helices ] = i

           end
        elseif ( within_helix == true ) then

            -- end of a helix
           
            within_helix = false
            helix_ends [ n_helices ] = i -1
        end
    end    -- for i
  
    if ( within_helix == true ) then
      helix_ends [ n_helices ] = n_residues
    end

end


function IsWithinASelectedHelix ( residue )

    for i = 1 , n_helices do
        if ( use_helix [ i ] == true ) then
           if ( ( residue >= helix_starts [ i ] ) and ( residue <= helix_ends [ i ] ) ) then
                return true
           end
        end
    end

    return false

end

function ConvertToLoop ( first , last )

    for  k = first , last do
        if ( original_secondary_structure [ k ] ~= "L" ) then
            if ( IsWithinASelectedHelix ( k ) == false ) then
                selection.DeselectAll ()
                selection.SelectRange ( k , k )
                structure.SetSecondaryStructureSelected ( "L" )
            end
        end
    end
end

function pseudorandom ( score )

    -- Returns a pseudorandom number >= 0 and < 1.
    -- Based on the fractional  part of the  score

    if ( score >= 0 ) then
      return  score % 1
     else
      return (-score ) % 1
    end

end

function GetListOfFixedResidues ()

    for i = 1 , n_residues do
        fixed_residues [ i ] = false
    end

    for i = 1 , n_residues do
        
         seg_backbone_frozen, seg_sidechain_frozen = freeze.IsFrozen ( i )

         if ( seg_backbone_frozen == true ) then
            fixed_residues [ i ] = true
         end

         s = structure.IsLocked ( i )
    
         if ( s == true ) then 
           fixed_residues [ i ] = true
         end

    end

end

function IsHelixFrozen ( start_idx , end_idx )

    for i = start_idx , end_idx do
        if ( fixed_residues [ i ] == true ) then
            return true
        end
    end

    return false

end

function ConstructListOfResiduesWithinInnerCylinder ( start_idx , end_idx )

    for i = 1 , n_residues do
        inner_cylinder [ i ] = false
    end

    for  i = 1 , n_residues do
         for j = start_idx , end_idx do
             if ( structure.GetDistance ( i , j ) < inner_cylinder_radius ) then
                inner_cylinder [ i ] = true
             end
        end
    end

end

function SelectInnerCylinder ()

    selection.DeselectAll ()
 
    for i = 1 , n_residues do
        if ( inner_cylinder [ i ] == true ) then
            selection.Select ( i )
        end
    end

end

function ConstructListOfResiduesWithinOuterCylinder ( start_idx , end_idx )

    for i = 1 , n_residues do
        outer_cylinder [ i ] = false
    end

     for  i = 1 , n_residues do
         for j = start_idx , end_idx do
             if ( structure.GetDistance ( i , j ) < outer_cylinder_radius ) then
                outer_cylinder [ i ] = true
             end
        end
    end

end

function SelectOuterCylinder ()

    selection.DeselectAll ()
 
    for i = 1 , n_residues do
        if ( outer_cylinder [ i ] == true ) then
            selection.Select ( i )
        end
    end

end

function WiggleNudge ( init_score )

    save.Quicksave ( kTemp )

    structure.WiggleSelected ( kWiggleDuration )
    score = GetScore ()
 
    if ( score < init_score ) then
        save.Quickload ( kTemp )   -- Filters can cause reduction in score
        score = init_score
    end

    save.Quicksave ( kTemp )
    score_in_temp = score

    behavior.SetClashImportance ( 0.1 )
    structure.WiggleSelected ( 1 )

    behavior.SetClashImportance ( 1 )
    structure.WiggleSelected ( kWiggleDuration )
    
    score = GetScore ()
    if ( score < score_in_temp ) then
         save.Quickload ( kTemp )   -- Filters can cause reduction in score
         score = score_in_temp
    end
 
   return score

end


function SelectBestPostRebuild ()

    save.Quickload ( kBestPostRebuild_a )
    structure.WiggleSelected ( kWiggleDuration )  
    score_a = GetScore ()

    save.Quicksave ( kBestPostRebuild_a_post_wiggle )
 
    save.Quickload ( kBestPostRebuild_b )
    structure.WiggleSelected ( kWiggleDuration )  
    score_b = GetScore ()

    if ( score_a > score_b ) then
        save.Quickload ( kBestPostRebuild_a_post_wiggle )
        return score_a
      else
        return score_b
    end

end

function ShakeLowCIWiggle ( init_score )

    save.Quicksave ( kTemp )
    
    behavior.SetClashImportance ( 0.10 )
    structure.ShakeSidechainsSelected ( 1 )

    behavior.SetClashImportance ( 1 )
    structure.WiggleSelected ( kWiggleDuration )

    score = GetScore ()
    
    if ( score <  init_score ) then
       save.Quickload ( kTemp )
       score = init_score 
    end
   
    return score

end

function ShakeWiggleNudge ( init_score )

    save.Quicksave ( kTemp )

    if ( mutate_not_shake == true ) then
        structure.MutateSidechainsSelected ( 1 )
      else
        structure.ShakeSidechainsSelected ( 1 )
    end
 
    score_after_shake = GetScore ()

    if ( score_after_shake < init_score ) then
        save.Quickload( kTemp )
        score_after_shake = init_score
    end

    return WiggleNudge ( score_after_shake )

end



function DetermineSpacers ( start_helix , end_helix )

    local	i
    local	ok

    start_idx = start_helix - loop_spacer

    if ( start_idx < 1 ) then
       start_idx = 1
    end

    i = start_helix - 1
    ok = true
    while ( i >= start_idx and ok == true ) do
        if ( structure.IsLocked ( i ) == true ) then
           ok = false
           start_idx = i + 1
         else
            i = i -1
        end
    end

    end_idx = end_helix + loop_spacer

    if ( end_idx > n_residues ) then
        end_idx = n_residues
    end

    i = end_helix + 1
    ok = true
    while ( i <= end_idx and ok == true ) do
         if ( structure.IsLocked ( i ) == true ) then
           ok = false
           end_idx = i - 1
         else
            i = i +1
        end
    end

    return start_idx , end_idx

end

function ConstructSpacers ( start_idx , start_helix , end_helix , end_idx )

    if ( start_helix > 1 ) then
        ConvertToLoop ( start_idx , start_helix - 1 )
    end

    if ( end_helix < n_residues ) then
        ConvertToLoop ( end_helix + 1 , end_idx )
    end

end

function RebuildHelix ( helix_index , start_helix , end_helix  )

    best_score_after_rebuild_and_shake_a = -99999
    best_score_after_rebuild_and_shake_b = -99999
   
    improvement_made = false
    
    rb = rb + 1

    start_idx , end_idx = DetermineSpacers ( start_helix , end_helix )

    save.Quickload (  kOriginalStructureOrNewBest )

    ConstructSpacers ( start_idx , start_helix , end_helix , end_idx )

    save.Quicksave (  kBestWithSpacers )
  
    ConstructListOfResiduesWithinInnerCylinder ( start_idx , end_idx )
    ConstructListOfResiduesWithinOuterCylinder ( start_idx , end_idx )

    print ( "rb : " .. rb .. " (" .. start_helix .. "-" .. end_helix .. ")" )
 
    for i = 1 , n_rebuilds do

        if ( i > 1 ) then
            save.Quickload (  kBestWithSpacers )
        end

        selection.DeselectAll ()
        selection.SelectRange ( start_idx , end_idx )

        structure.RebuildSelected ( 1 )
        score_after_rebuild = GetScore ()
 
        SelectInnerCylinder ()

        structure.ShakeSidechainsSelected ( 1 )
        structure.WiggleSelected ( 1 )

        score_after_shake_wiggle = GetScore ()

        if ( score_after_shake_wiggle > math.min ( best_score_after_rebuild_and_shake_a , best_score_after_rebuild_and_shake_b ) ) then
	     
            if ( best_score_after_rebuild_and_shake_b < best_score_after_rebuild_and_shake_a ) then
                best_score_after_rebuild_and_shake_b = score_after_shake_wiggle
                save.Quicksave ( kBestPostRebuild_b )
             else
                best_score_after_rebuild_and_shake_a = score_after_shake_wiggle
	        save.Quicksave ( kBestPostRebuild_a )
            end

        end

    end

    SelectOuterCylinder ()
 
    c_score = SelectBestPostRebuild ()

    score_below_best = best_score - c_score

    if ( score_below_best < pw_threshold_value ) then

        d_score = ShakeWiggleNudge ( c_score )

        if ( ( d_score > best_score ) and 
               ( test_for_credit == false or creditbest.AreConditionsMet () == true ) ) then

            e_score = ShakeLowCIWiggle ( d_score )

             print ( "     " .. r3 ( -score_below_best ) .. "  " .. r3 ( d_score - c_score )  .. "  " .. r3 ( e_score - d_score ) )
             improvement_made = true

            best_score = e_score

            save.LoadSecondaryStructure () 

            save.Quicksave ( kOriginalStructureOrNewBest )
            print ( "Improvement to " ..  r3 ( best_score ) )
          else
            print ( "     " .. r3 ( -score_below_best ) .. "  " .. r3 ( d_score - c_score ) )
 
        end

      else
       print ( "     " .. r3 ( -score_below_best ) )
    end

    save.LoadSecondaryStructure ()

end

function GetParameters ()

    local dlog = dialog.CreateDialog ( "Helix rebuild 5.1" )

    dlog.loop_spacer = dialog.AddSlider ( "Loop spacer" , loop_spacer , 0 , 6 , 0 )  
  
    for i = 1 , n_helices do
        dlog [ "helix" .. i ] = dialog.AddCheckbox ( helix_starts [ i ] .. "-" .. helix_ends [ i ]  , true )  
    end

    dlog.n_rebuilds = dialog.AddSlider ( "Rebuilds" , n_rebuilds , 1 , 20 , 0 )  
  
    dlog.pw_threshold = dialog.AddSlider ( "Post wiggle threshold" , pw_threshold_value , 0 , 200 , 0 )  
    
    design_puzzle = IsPuzzleMutable ()

    if ( design_puzzle == true ) then
        dlog.mutate= dialog.AddCheckbox ( "Mutate not shake" , true )  
    end

    dlog.credit_check = dialog.AddCheckbox ( "Check conditions met " , test_for_credit )  

    dlog.pw_threshold = dialog.AddSlider ( "Post wiggle threshold" , pw_threshold_value , 0 , 200 , 0 )  
    
    if ( DoesPuzzleHaveSlowFilters () == true ) then
        score_type = 2
    end

    dlog.score_type = dialog.AddSlider ( "Score type" , score_type , 1 , 2 , 0 )  
    dlog.tp = dialog.AddLabel ( "1 = Normal : 2 = Normal for Slow Filters"  )

    dlog.ok = dialog.AddButton ( "OK" , 1 )
    dlog.cancel = dialog.AddButton ( "Cancel" , 0 )
  
    if ( dialog.Show ( dlog ) > 0 ) then
    
        loop_spacer = dlog.loop_spacer.value

        for i = 1 , n_helices do
            use_helix [ i ] = dlog [ "helix" .. i ].value
        end
    
        if ( design_puzzle == true ) then
            mutate_not_shake = dlog.mutate.value
        end

        test_for_credit = dlog.credit_check.value

        n_rebuilds = dlog.n_rebuilds.value
        pw_threshold_value = dlog. pw_threshold.value
         score_type = dlog.score_type.value
    
        return true
      else
        return false
    end

end

function main ()

    print (  "Helix rebuild 5.1" )

    band.DisableAll ()

    n_residues = structure.GetCount ()

    for i = 1, n_residues do
         original_secondary_structure [ i ] = structure.GetSecondaryStructure ( i )
    end

    save.SaveSecondaryStructure () 

    behavior.SetClashImportance ( 1 )

    GetHelices ()

    GetListOfFixedResidues ()

   -- Delete locked/frozen helices

    for i = n_helices , 1 , -1 do 
        if ( IsHelixFrozen ( helix_starts [ i ] , helix_ends [ i ] ) == true ) then
             table.remove ( helix_starts , i )
             table.remove ( helix_ends , i )
        end
    end

    n_helices = #helix_starts

    print ( n_helices .. " helices" )

    qs10_best_score = 0

    original_slow_filters_setting = behavior.GetSlowFiltersDisabled ()

    if ( GetParameters () == false ) then
       print ( "error" )
       error ()
    end

    best_score = GetScore ()
    print (  "Start score : " .. r3  ( best_score )  )

    if ( score_type == 1 ) then
        print (  "Score type : Normal" )
      elseif ( score_type == 2 ) then
        print (  "Score type : Normal/Slow Filters" )
    end

    -- Delete unused helices

    for i = n_helices , 1 , -1 do 
        if ( use_helix [ i ] == false ) then
             table.remove ( helix_starts , i )
             table.remove ( helix_ends , i )
        end
    end

    n_helices = #helix_starts

    if ( n_helices == 0 ) then
       print ( "No helix selected" )
       error ()
    end

    for i = 1 , n_helices  do 
         print ( "Helix " .. i .. " : (" .. helix_starts [ i ] .. "-" .. helix_ends [ i ] .. ")" )
    end

    print ( "Loop spacer " .. loop_spacer )
    print ( n_rebuilds .. " rebuilds" )

    rb = 0
    save.Quicksave ( kOriginalStructureOrNewBest )

    while ( true ) do
        for i = 1 , n_helices do 
            RebuildHelix ( i , helix_starts [ i ] , helix_ends [ i ] )
        end
    end

end

function cleanup ()
   
    print ( "Cleaning up" )
    behavior.SetClashImportance ( 1.0 )
    save.Quickload ( kOriginalStructureOrNewBest )

    behavior.SetSlowFiltersDisabled ( original_slow_filters_setting )

    band.EnableAll ()

end

--main ()
xpcall ( main , cleanup )

Comments

[spvincent]

As 5.0 but fixed some problems related to Secondary structure (thanks LociOiling)

This script is probably most useful in the early/middle game (although the chess analogy can be pushed too far). Best used at Low or Auto Wiggle Power I think: the script never terminates.

Algorithm outline

For each helix
    For however many rebuilds specified
        Bracket it with a loop on either end
        Rebuild once
        Shake and wiggle briefly
        Record score
    end
    Take two best poses from above
    Wiggle each
    Take the best scoring pose, shake (optionally mutate) and wiggle.
    If the score looks as if it might result in a new best
        Wiggle at Low CI
        Wiggle
        If score is better than the current best  
            Shake at Low CI
            Wiggle
        end
        Record any gain
    end
end


Selection is restricted to the local vicinity of the helix for the sake of efficiency.
See values of inner_cylinder_radius and outer_cylinder_radius, which are probably unnecessarily conservative.

Loop spacer

Specifies the length of the loops at either end of the helix. The greater the value, the more freedom there is for the helix to adopt new configurations but the less likely you are to get small refinements.

Helix List

Initially all are selected. Helices with locked or frozen backbones will not appear in this list: frozen sidechains are allowable though.

Rebuilds

How many times to rebuild each helix

Mutate not shake

For puzzles with mutable residues only

Post wiggle threshold

Threshold that specifies the maximum allowable difference between the score after shake/wiggle and the best score to allow before proceeding with the mini-fuses. An optimization: the default value is perhaps a bit permissive.

Check conditions met

If set, check that conditions are met before accepting any improvement. For puzzles with RMSD conditions, etc.

Score type

Default is Normal. Normal/Slow Filters is for slow design/symmetry puzzles (for such puzzles the score type defaults to this mode): it toggles slow filters apart from scoring.

When running, the script will print out from one to three values after each helix rebuild set. The first value, which is usually negative, shows the difference between the score after Shake(or Mutate)/Wiggle and the best current score. This could be used to fine tune the threshold value above. The second value (which will only happen if the first value is numerically below the threshold value) will show the gain from LowCI Wiggle/Wiggle. The third value, if present, shows the gain, if any, from Low CI Shake/WiggleL in this case there will be a score improvement.

[GreenSlugg]

Thank you for sharing this. I am still new at this, and this looks like it will help.