Recipe: Helix Rebuild 2

created by spvincent

Profile

• Name: Helix Rebuild 2
• ID: 45788
• Shared with: Public
• Parent: None
• Children:
  • Helix Rebuild 2.01
  • Helix Rebuild 2
  • Helix Rebuild 2 nc
• Created on: March 21, 2013 at 00:21 AM UTC
• Updated on: March 21, 2013 at 00:21 AM UTC
• Description:

  See first comment

Code

-- Globals

original_secondary_structure = {}

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

n_residues = 0

loop_spacer = 3
co_rebuild = false

clash_importance_during_rebuild = 0.3
n_rebuilds = 5

fuze_threshold = 4

       -- For design

mutate_not_shake = false

-- Quicksave slots

kOriginalStructureOrNewBest = 1	  -- the starting structure, or any subsequent improvement, will be stored in this quicksave slot

kTemp = 5
						
kQs10 = 10                                                -- the rebuilt structure that comes closest in score to the original without actually exceeding it
                                                                    -- will be stored here


function roundto3 ( i )

-- printing convenience

   return i - i % 0.001

end

function GetScore ()

    score = current.GetEnergyScore () 

    return score

end

function IsPuzzleMutable ()

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

    return false

end

function get_helices ()

    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 )

    -- When
    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.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 MiniFuse ()

    selection.SelectAll ()

    score_in_kTemp = GetScore()
    save.Quicksave ( kTemp)

    selection.SelectAll ()
    behavior.SetClashImportance  ( 0.07 )

    structure.ShakeSidechainsSelected ( 1 )
 
    behavior.SetClashImportance ( 1 )
    structure.WiggleSelected ( 8 )

    score = GetScore()

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

end


function nudge (  score )

    selection.SelectAll ()
    recentbest.Save ()
    behavior.SetClashImportance ( 0.2  + 0.2 * pseudorandom ( score ) )
    structure.WiggleSelected ( 1 )
    behavior.SetClashImportance ( 1 )
    structure.WiggleSelected ( 8 )
    recentbest.Restore ()
 end


function  ShakeWiggleShakeNudge ()

     -- returns the score after doing a SWSW:  short-circuiting if things don't look promising

    if ( false ) then
        structure.MutateSidechainsSelected ( 1 )
      else
        structure.ShakeSidechainsSelected ( 2 )
    end
 
    score_after_first_shake = GetScore ()

    structure.WiggleSelected ( 12 )
    score_after_wiggle = GetScore ()

    if ( score_after_wiggle - score_after_first_shake  < 10 and best_score - score_after_wiggle > 30 ) then
        --    The wiggle got stuck and didn't achieve anything
        nudge ( score_after_wiggle )
        score_after_wiggle = GetScore ()
    end
    
    if ( mutate_not_shake == true ) then
        structure.MutateSidechainsSelected ( 1 )
      else
        structure.ShakeSidechainsSelected ( 1 )
    end
    
    score_after_second_shake = GetScore ()

    if ( score_after_second_shake - score_after_wiggle > 0.5 ) then
        nudge ( score_after_second_shake )
 
        score = GetScore  ()

        return  score
     else
        return  score_after_second_shake
    end

end


function ConstructSpacers ( start_helix , end_helix )

    start_idx = start_helix - loop_spacer

    if ( start_idx < 1 ) then
       start_idx = 1
    end

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

    end_idx = end_helix + loop_spacer

    if ( end_idx > n_residues ) then
        end_idx = n_residues
    end

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

    return start_idx , end_idx

end

function rebuild_helix ( start_helix , end_helix  )

    improvement_made = false

    save.Quickload ( kOriginalStructureOrNewBest )
 
    rb = rb + 1

    best_score = GetScore ()
    selection.DeselectAll ()


    if ( co_rebuild == true ) then

        print ( "rb : " .. rb )

        for i = 1 , n_helices do
            if ( use_helix [ i ] == true ) then
                start_idx , end_idx = ConstructSpacers ( helix_starts [ i ] , helix_ends [ i ] )
                selection.SelectRange ( start_idx , end_idx )
            end
        end

      else

        print ( "rb : " .. rb .. " (" .. start_helix .. "-" .. end_helix .. ")" )

        start_idx , end_idx = ConstructSpacers ( start_helix , end_helix )
        selection.SelectRange ( start_idx , end_idx )

    end

    behavior.SetClashImportance ( clash_importance_during_rebuild )
    recentbest.Save ()

    structure.RebuildSelected ( 1 )
    score_after_rebuild = GetScore ()
    recentbest.Save ()

    if ( math.abs ( score_after_rebuild - best_score ) < 1e-5 ) then
               
        -- If  the scores are still equal we probably have a locked segment

        return false
    
    end

    structure.RebuildSelected ( 5 )
    recentbest.Restore ()
    behavior.SetClashImportance ( 1.0 )
 
    selection.SelectAll ()

    curr_score = ShakeWiggleShakeNudge ()

    if ( curr_score > best_score - fuze_threshold ) then
        MiniFuse ()
        print ( "  Fuze gain : " .. roundto3 ( GetScore () - curr_score ) )
    end

    curr_score = GetScore ()

    if ( curr_score > best_score ) then

        improvement_made = true

        best_score = curr_score

        save.LoadSecondaryStructure () 

        save.Quicksave ( kOriginalStructureOrNewBest )
        print ( "Improvement to " ..  roundto3 ( best_score ) )
                     
    end

    curr_score = GetScore ()

    if (  curr_score > qs10_best_score  and improvement_made == false ) then
      
        qs10_best_score = curr_score
 
        save.Quicksave ( kQs10 )

        print ( "Storing " .. roundto3 ( qs10_best_score ) .. " in " .. kQs10 )

    end

    save.LoadSecondaryStructure ()

    return true

end

function get_parameters ()

  local dlog = dialog.CreateDialog ( "Helix rebuild 2" )

  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.co_rebuild = dialog.AddCheckbox ( "Co-rebuild" , co_rebuild )  

  dlog.n_rebuilds = dialog.AddSlider ( "Rebuilds" , n_rebuilds , 1 , 20 , 0 )  
  dlog.ci = dialog.AddSlider ( "Clash importance" , clash_importance_during_rebuild , 0 , 1.0 , 2 )  
  
  dlog.fzth = dialog.AddSlider ( "Fuze threshold" , fuze_threshold , 0 , 20 , 0 )  
  design_puzzle = IsPuzzleMutable ()

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

  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
    
    co_rebuild = dlog.co_rebuild.value

    if ( design_puzzle == true ) then
       mutate_not_shake = dlog.mutate.value
    end

    n_rebuilds = dlog.n_rebuilds.value
    clash_importance_during_rebuild = dlog.ci.value
    
    fuze_threshold = dlog.fzth.value

    return true
  else
     return false
   end

end

function main ()

    print (  "Helix  rebuild 2" )

    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 )

    best_score = GetScore ()
    print (  "Start score : " .. roundto3  ( best_score )  )

    get_helices ()

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

    qs10_best_score = 0

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

    -- Check that at least one helix was selected

    found = false
    i = 1
    while ( i <= n_helices and found == false ) do
      if ( use_helix [ i ] == true ) then
         found = true
      end
      i = i + 1
    end

    if ( found == false ) then
       print ( "No helix selected" )
       error ()
    end

    rb = 0
    save.Quicksave ( kOriginalStructureOrNewBest )

    while ( true ) do
        for i = 1 , n_helices do 
            if ( use_helix [ i ] == true ) then
                rebuild_helix ( helix_starts [ i ] , helix_ends [ i ] )
            end
        end
    end

end

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

    band.EnableAll ()

end

--main ()
xpcall ( main , cleanup )

Comments

[spvincent]

This script is probably most usefully used in the early/middle game (although the chess analogy can be pushed too far).

Algorithm outline

For each helix, bracket it with a loop on either end, rebuild it and the loop spacers several times at low CI, take the highest scoring result and then do Shake, Wiggle, Shake, nudging the protein slightly if the wiggle gets stuck. If the score is reasonably close to the best score, do a Fuze.

Loop spacer

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

Helix list

A list of check boxes showing the helices in the protein.

Corebuild

If checked, all selected helices will be rebuilt together. this setting was intended for the case where there were two antiparallel helices that might beneficially be rebuilt together but I've yet to see a case where it produces a gain.

Number of rebuilds

How many times to rebuild the helix before Shaking, etc.

Clash Importance

The CI during rebuild

Fuze Threshold

How many points within the original score before attempting a Fuze

Mutate not Shake

For design puzzles only: If set does a Mutate rather a Shake (i.e. does Shake/Wiggle/Mutate)