Recipe: Jolter 1.0

created by spvincent

Profile

• Name: Jolter 1.0
• ID: 101691
• Shared with: Public
• Parent: Jo;ter 1.0
• Children: None
• Created on: December 17, 2015 at 03:05 AM UTC
• Updated on: December 17, 2015 at 03:05 AM UTC
• Description:

  See first comment

Code

best_score = 0
min_residue = 0
max_residue = 0
n_residues = 0
post_rebuild = 3
score_type = 1

original_slow_filters_setting = 0

kCurrBaseStructure = 1
curr_base_score = 0

kBestPostRebuild = 2
kTemp = 3

n_rebuilds = 8
rejection_threshold = 16

kMaxSphereDistance = 14

SphereSegList = {}				-- store list of residues within kMaxSphereDistance of any residue in the segment.
							-- speeds things up when shaking


-- SS info

ss_starts = {}
ss_ends  = {}
ss_types = {}

helix_spacer = 3
sheet_spacer = 2
loop_spacer = 1

kMinSSLength = 3

function r3 ( x )

-- Round to 3 decimal places

  t  = 10 ^ 3

  return math.floor ( x*t + 0.5 ) /  t 

end

function GetScore ()

    if ( score_type == 1 ) then

        score = current.GetScore () 

    elseif ( score_type == 2 ) then

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

    end

    return score

end

function GetSecondaryStructures ()

    curr_s_type = false
  
    for i = 1, n_residues do

        s_type = structure.GetSecondaryStructure ( i )
    
        if ( i == 1 ) then

            ss_starts [ 1 ] = i
            ss_types [ 1 ] = s_type

         elseif  ( s_type ~= prev_s_type ) then

             ss_ends [ #ss_ends + 1 ] = i - 1
            
             ss_starts [ #ss_starts + 1 ] = i
             ss_types [ #ss_types + 1  ] = s_type

        end

        prev_s_type = s_type
          
    end

    ss_ends [ #ss_ends + 1 ] = n_residues

end

function SelectSphere ()

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

end


function ConstructListOfResiduesWithinRange ( start_idx , end_idx )

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

   for j = start_idx , end_idx do
      for  i = 1 , n_residues do
         if ( ( i >= start_idx and i <= end_idx ) or
             ( structure.GetDistance ( i , j ) < kMaxSphereDistance ) ) then
            SphereSegList [ i ] = true
        end
    end
  end

end

function NudgeWiggle ()

    selection.SelectAll ()

    score_in_kTemp = GetScore ()
    save.Quicksave ( kTemp)

    behavior.SetClashImportance ( 0.5 )
    structure.WiggleSelected ( 1 )
    behavior.SetClashImportance ( 1 )
    structure.WiggleSelected ( 6 )

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

end


function Rebuild ( start_idx , end_idx )

    ConstructListOfResiduesWithinRange ( start_idx , end_idx )

    improvement_made = false
    best_post_rebuild_score = -999999

    i = 1

    while ( ( i <= n_rebuilds ) and ( improvement_made == false ) ) do

        save.Quickload ( kCurrBaseStructure )

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

        structure.RebuildSelected ( 1 )

        SelectSphere ()
        structure.ShakeSidechainsSelected ( 1 )

        if ( post_rebuild >= 2 ) then

            selection.SelectAll ()
  
            score_before_wiggle = GetScore ()
            structure.WiggleSelected ( 10 )
            score_after_wiggle = GetScore ()

            if ( score_after_wiggle - score_before_wiggle  < 1 ) then
  
                --    The wiggle got stuck and didn't achieve anything

                NudgeWiggle ()
            end

            if ( post_rebuild >= 3 ) then

                score_before_sm = GetScore ()

                SelectSphere ()
                if ( post_rebuild == 3 ) then
                   structure.ShakeSidechainsSelected ( 1 )
                  else
                   structure.MutateSidechainsSelected ( 1 )
                end

                score_after_sm = GetScore ()
 
                if ( score_after_sm - score_before_sm  > 1e-3 ) then
  
                    score_before_wiggle = score_after_sm
                    structure.WiggleSelected ( 10 )
                    score_after_wiggle = GetScore ()

                    if ( score_after_wiggle - score_before_wiggle < 1 ) then
  
                        --    The wiggle got stuck and didn't achieve anything

                        NudgeWiggle ()
                    end

                 end

            end   -- ( post_rebuild >= 3 )

        end   -- ( post_rebuild >= 2 )

        score = GetScore ()

        if ( score > best_post_rebuild_score) then

             best_post_rebuild_score = score
             save.Quicksave ( kBestPostRebuild )

             if ( score > curr_base_score ) then
                improvement_made = true
             end

            --print (  "   New best post rebuild score " .. r3 ( score ) )
         end

        i = i + 1

     end

    if ( best_post_rebuild_score > curr_base_score - rejection_threshold ) then

        save.Quickload ( kBestPostRebuild )

        save.Quicksave ( kCurrBaseStructure )
        curr_base_score =  best_post_rebuild_score
 
        print (  "   new working score " .. r3 ( curr_base_score ) )
       
    end
  
end

function Go ()

    for j = 1 , 2 do

        for i = j , #ss_starts , 2 do

            start_idx = ss_starts [ i ]
            end_idx = ss_ends [ i ]
            
            print ( "rb " .. start_idx .. "-" .. end_idx .. " (" .. ss_types [ i ] .. ")" )

            Rebuild ( start_idx , end_idx )

         end

    end

end

function AddSpacers ()

    for i = 1 , #ss_starts do

        start_idx = ss_starts [ i ]
        end_idx = ss_ends [ i ]
            
        if ( ss_types [ i ] == "H" ) then
            start_idx = start_idx - helix_spacer
            end_idx =  end_idx + helix_spacer
         elseif ( ss_types [ i ]  == "E" ) then
            start_idx = start_idx - sheet_spacer
            end_idx =  end_idx + sheet_spacer
         elseif ( ss_types [ i ]  == "L" ) then
            start_idx = start_idx - loop_spacer
            end_idx =  end_idx + loop_spacer
        end

        ss_starts [ i ] = math.max ( 1 , start_idx )
        ss_ends [ i ] = math.min ( n_residues , end_idx )

    end

end

function BackboneFrozen ( start_idx , end_idx )

    for i = start_idx , end_idx do

        seg_backbone_frozen, seg_sidechain_frozen = freeze.IsFrozen ( i )

        if ( seg_backbone_frozen == true ) then
            return 1
        end

    end

    return 0

end

function FilterSS ()

-- Delete any Secondary structures that are outside the range, locked, or consist of small loops

    for i = #ss_types , 1 , -1 do
    
        if ( ( ss_starts [ i ] > max_residue ) or 
             ( ss_ends [ i ] < min_residue ) or 
             ( BackboneFrozen ( ss_starts [ i ] , ss_ends [ i ] ) == 1 ) or 
              (  ss_ends [ i ] - ss_starts [ i ]  + 1 <  kMinSSLength ) ) then 
           table.remove ( ss_starts , i )
           table.remove ( ss_ends , i )
           table.remove ( ss_types , i )
        end

    end

end


function GetParameters ()

    local dlog = dialog.CreateDialog ( "Jolter 1.0" )

    dlog.min_residue = dialog.AddSlider ( "Min residue" , 1 , 1 , n_residues , 0 )  
    dlog.max_residue = dialog.AddSlider ( "Max residue" , n_residues , 1 , n_residues , 0 )  

    dlog.n_rebuilds= dialog.AddSlider ( "N Rebuilds" , n_rebuilds , 1 , 30 , 0 )  
  
    dlog.post_rebuild = dialog.AddSlider ( "Post rebuild" , post_rebuild , 1 , 4 , 0 )  
    dlog.pr = dialog.AddLabel ( "1 = Sh : 2 = Sh/W : 3 = Sh/W/Sh/W : 4 = Sh/W/Mu/W"  )

    dlog.rejection_threshold = dialog.AddSlider ( "Rejection threshold" , rejection_threshold , 0 , 100 , 0 )  
    dlog.helix_spacer = dialog.AddSlider ( "Helix spacer" , helix_spacer , 0 , 4 , 0 )  
    dlog.sheet_spacer = dialog.AddSlider ( "Sheet spacer" , sheet_spacer , 0 , 4 , 0 )  
    dlog.loop_spacer = dialog.AddSlider ( "Loop spacer" , loop_spacer , 0 , 4 , 0 )  

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

    dlog.ok = dialog.AddButton ( "OK" , 1 )
    dlog.cancel = dialog.AddButton ( "Cancel" , 0 )

    if ( dialog.Show ( dlog ) > 0 ) then
    
       min_residue = dlog.min_residue.value
       max_residue = dlog.max_residue.value
       n_rebuilds = dlog.n_rebuilds.value
       post_rebuild = dlog.post_rebuild.value
       rejection_threshold = dlog.rejection_threshold.value
       helix_spacer = dlog.helix_spacer.value
       sheet_spacer = dlog.sheet_spacer.value
       loop_spacer = dlog.loop_spacer.value
       score_type = dlog.score_type.value
       return true
    else
       return false
   end

end

function main ()

    print ( "Jolter 1.0" )

    n_residues = structure.GetCount ()

    save.Quicksave ( kCurrBaseStructure )
    curr_base_score = GetScore ()

    print ( "Start score " .. r3 ( curr_base_score ) )

    behavior.SetClashImportance ( 1 )
    original_slow_filters_setting = behavior.GetSlowFiltersDisabled ()

    if ( GetParameters () == false ) then
      return
    end

    max_residue = math.min ( n_residues , max_residue )
    min_residue = math.max ( 1 , min_residue )
    if ( max_residue < min_residue ) then
        print ( "Range error." )
        print ( "Max residue (" .. max_residue .. ") must be greater than or equal to Min residue (" ..  min_residue .. ")" )
        return
    end

    print  ( "Range " .. min_residue .. " to " .. max_residue )
    print ( "N rebuilds " .. n_rebuilds )
    print ( "Rejection threshold " .. r3 ( rejection_threshold ) )
    print ( "Helix spacer " .. helix_spacer )
    print ( "Sheet spacer " .. sheet_spacer )
    print ( "Loop spacer " .. loop_spacer )

    if ( post_rebuild == 1 ) then
        print ( "Post rebuild : Shake" )
    elseif ( post_rebuild == 2 ) then
        print ( "Post rebuild : Shake/Wiggle" )
    elseif ( post_rebuild == 3 ) then
        print ( "Post rebuild : Shake/Wiggle/Shake/Wiggle" )
    elseif ( post_rebuild == 4 ) then
        print ( "Post rebuild : Shake/Wiggle/Mutate/Wiggle" )
    end

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

    print ()

    GetSecondaryStructures ()

--for i = 1 , #ss_types do
--print ( ss_starts [ i ] .. "  " .. ss_ends [ i ] .. "  " .. ss_types [ i ] )
--end

    AddSpacers ()
    FilterSS ()

--print ( "Post Filter" )
--for i = 1 , #ss_types do
--print ( ss_starts [ i ] .. "  " .. ss_ends [ i ] .. "  " .. ss_types [ i ] )
--end
   
    while true do
        Go ()
    end

end

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

    if ( score_type == 2 ) then
        behavior.SetSlowFiltersDisabled ( original_slow_filters_setting )
    end

end

--main ()
xpcall ( main , cleanup )

Comments

[spvincent]

Jolter is a rebuild script that's designed, as the name suggests, to jolt the protein out of a local minimum (that's the intent anyway), although it does seem useful in other circumstances. It successively rebuilds alternate structural elements in the protein, being prepared to accept a small loss in score after the usual quota of shakes and wiggles that normally follow a rebuild (gains are also accepted, needless to say).

The script never terminates: it's best run overnight or at least for a couple of hours. After cancelling the script you can start from the existing position, or, since the score meanders up and down when running the script. Suggested followup would be to run an Idealize script followed by the rebuilder of your choice.

Algorithm outline

Get list of secondary structure elements (helix, sheet, loop)

For each element (going alternately)
Repeat 8 times (value of N rebuilds below)
Rebuild element
Shake/Wiggle etc (Post Rebuild below)
end

Take best scoring position from above
If score is better than the current score minus the rejection threshhold then
make this the new current position
end
end

Min residue: max residue

Used to define the region of the protein to be rebuilt. Any secondary structure element that lies at least partially within this region will be processed. An element that contains a residue with a frozen backbone will not be processed.

N Rebuilds

How many times to rebuild each structure. Reducing this value may result in a more structurally diverse result, albeit at the likely expense of a poorer score.

Post Rebuild

The actions to be taken after each rebuild, The default is Shake/Wiggle/Shake/Wiggle (with nudges at low CI if things get stuck) but for design puzzles number 4 (Shake/Wiggle/Mutate/Wiggle) is likely preferable.

Rejection Threshold

Specifies how big a loss is permissible. The larger the value the greater the change in structure that will be allowed at the possiblee expense of score

Setting this to zero means that only gains will be permitted: useful in the earlier stages.

Helix spacer, Sheet spacer, Loop spacer

When rebuilding, specifies the length of a spacer at either end of the structural element that will be included in the rebuild. So if the value of Helix spacer were 3, then when working on a helix from 63 to 75, the actual rebuild length would be 60 to 78.

Score type

If set to 2, toggles filters off except when determining the score. For better performance on slow design puzzles.

[CouwebMHS]

WOW!