Recipe: HNetwork Probe 1.0

created by spvincent

Profile

• Name: HNetwork Probe 1.0
• ID: 102977
• Shared with: Public
• Parent: None
• Children: None
• Created on: January 01, 2019 at 02:34 AM UTC
• Updated on: January 01, 2019 at 02:34 AM UTC
• Description:

  See first comment

Code

polar_aas = "stnqdekrhyw"
n_polar_aas = 0

n_residues = 0
first_qs_slot = 13
next_qs_slot = 0
start_slot = 1

select_unfrozen = false
filter_threshold = 40
n_it = 0

mutate_list_ui = {}  -- will be a list of 1's & 0's for each residue. 1 means can mutate.  0 means don't mutate.

mutable_list = {}

filter_list = {}
init_filter_score = 0

function r3 ( x )

-- Round to 3 decimal places

  t  = 10 ^ 3

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

end

function GetFilterScore ()


     filter_bonus = filter.GetBonus ( "Hydrogen Bond Network" )
   
     return filter_bonus

end

function GetListOfMutablesUnfrozen ()

    for i = 1 , n_residues do

       seg_backbone_frozen, seg_sidechain_frozen = freeze.IsFrozen ( i )

        if ( ( seg_sidechain_frozen == false ) and
             ( seg_backbone_frozen == false )  and
             ( structure.IsMutable ( i ) == true ) ) then
             table.insert ( mutable_list , i )
        end
    end

end

function  GetListOfMutablesSelected ()

    for i = 1 , n_residues do

        seg_backbone_frozen, seg_sidechain_frozen = freeze.IsFrozen ( i )

        if ( ( seg_sidechain_frozen == false ) and
             ( mutate_list_ui [ i ] == 1  )  and
             ( structure.IsMutable ( i ) == true ) ) then
             table.insert ( mutable_list , i )
        end
    end

end


-- getlist pinched from Loop Rebuild 9.0
-- http://www.lua.org/manual/5.2/manual.html#6.4 
-- helped make this function 11/16/17
function getlist(liststr)
   local newlist={}
   local i,ilo,ihi,idir,substr
   for i=1,n_residues do
      newlist[i]=0
   end -- for i

-- below reads from liststr a series of substr's
-- where each substr contains an integer
-- followed by one or more '-' signs
-- followed by an integer
   for substr in string.gmatch(liststr,"(%d+%-+%d+)") do
      -- substr includes one or more '-' characters in a row 
      
      -- below gets ilo & ihi from substr
      ilo=string.gsub(substr,"(%d+)%-+(%d+)","%1")+0
      ihi=string.gsub(substr,"(%d+)%-+(%d+)","%2")+0
      -- above gets ilo & ihi from substr
      
      idir=1 -- the increment to use from ilo to ihi
      if ilo>ihi then
         idir= -1
      end -- if ilo
      for i=ilo,ihi,idir do -- for i=ilo to ihi step idir
         if i>=1 and i<=n_residues then
            newlist[i]=1
         end -- if i
      end -- for i
   end -- for substr

-- below reads from liststr a series of substr's
-- where each substr contains an integer
   for substr in string.gmatch(liststr,"(%d+)") do
      i=substr+0 -- converts substr into the number i
      if i>=1 and i<=n_residues then
         newlist[i]=1
      end -- if i
   end -- for substr

   return newlist
end

function Init ()

    save.Quickload ( start_slot )
 
    for i = 1 , #mutable_list do

        k = math.random ( n_polar_aas ) 
        structure.SetAminoAcid ( mutable_list [ i ] , string.sub ( polar_aas , k , k  ) )
    end

    selection.SelectAll ()
    structure.WiggleSelected ( 2 , false , true )    -- sidechains

    init_filter_score = GetFilterScore ()
end

function PrintParameters ()

    print ( " n mutables " .. #mutable_list )
    print ( "Amino acids to use : " .. polar_aas )
end

function GetParameters ()

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

    dlog.use_unfrozen = dialog.AddCheckbox ( "Select unfrozen" , select_unfrozen ) 

    dlog.mutate_list = dialog.AddTextbox ( "Mutate segments" , "" )
    dlog.mlabela = dialog.AddLabel('List segs to mutate like 1-3,6,19-30,45-62')
 
    dlog.aa_list = dialog.AddTextbox ( "Amino acids" , polar_aas )
    dlog.filter_threshold = dialog.AddSlider ( "Filter threshold" , filter_threshold  , 1 , 200 , 0 )  

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

    if ( dialog.Show ( dlog ) > 0 ) then
    
        select_unfrozen = dlog.use_unfrozen.value  
        mutate_list_ui = getlist(dlog.mutate_list.value)
        polar_aas = dlog.aa_list.value
 
        filter_threshold = dlog.filter_threshold.value

        return true
      else
        return false
    end

end

function main ()

    n_residues = structure.GetCount ()

    save.Quicksave ( start_slot )
 
    if ( GetParameters () == false ) then
         return                -- graceful exit
    end

    n_polar_aas = string.len ( polar_aas )

    if ( select_unfrozen == true ) then
       GetListOfMutablesUnfrozen ()
     else
       GetListOfMutablesSelected ()
    end

    PrintParameters ()

    if ( #mutable_list  == 0 ) then
        print ( "No mutable residues found" )
        exit (0)
    end

    filter_list = filter.GetNames ()

    print ( "Filters" )
    print ( "" )

    for i = 1 , #filter_list do
      if ( filter_list [ i ] == "Hydrogen Bond Network" ) then
          filter.Enable ( filter_list [ i ] )
          print ( "Enabling " .. filter_list [ i ] )
        else
          filter.Disable ( filter_list [ i ] )
          print ( "Disabling " .. filter_list [ i ] )
      end

    end

    band.DisableAll ()
    undo.SetUndo ( false )

    init_filter_score = GetFilterScore ()
    math.randomseed ( os.time () )
 
    next_qs_slot = first_qs_slot

    Init ()
 
    while next_qs_slot < 100 do		-- basically forever

        n_it = n_it + 1
        i = math.random ( #mutable_list )

        k = math.random ( n_polar_aas ) 
        structure.SetAminoAcid ( mutable_list [ i ] , string.sub ( polar_aas , k , k  ) )
   
        selection.SelectAll ()

        --structure.ShakeSidechainsSelected ( 1 )
        structure.WiggleSelected ( 2 , false , true )    -- sidechains

        filter_score = GetFilterScore ()
  
        if ( filter_score > init_filter_score + filter_threshold ) then

             print ( "Found network ( gain " .. r3 ( filter_score - init_filter_score ) .. " ) storing in qs " .. next_qs_slot )
             save.Quicksave ( next_qs_slot )
             next_qs_slot = next_qs_slot + 1

             Init ()

        end
 
    end

    cleanup ()

end

function cleanup ()
   
    print ( "Cleaning up" )

    print ( "n_it " .. n_it )

    undo.SetUndo ( true )

    if ( next_qs_slot > first_qs_slot ) then

        print ( "Loading quick saves " .. first_qs_slot .. " to " .. next_qs_slot - 1  )
        for i = first_qs_slot , next_qs_slot - 1 do
            save.Quickload ( i )
        end
    end

    band.EnableAll ()
    filter.EnableAll ()

end

--main ()
xpcall ( main , cleanup )

Comments

[spvincent]

This is a script that's intended to help with creating Hydrogen Bond Networks. It's something of a blunt instrument but the resultant poses can help serve as a starting point for future work.

The idea is to make a limited selection of residues in an area where networks might plausibly form, randomly mutate them to amino acids that have either hydrogen bond donors or acceptors, wiggle the sidechains, and then, if any hydrogen bond networks form, store them in quicksave slots.

Selecting the residues to mutate.

Two ways this can be done: select unfrozen residues only or explicitly list the residues to mutate. Because of the fairly inefficient nature of this script, it's desirable to limit this number: I've found 20 or so to be a reasonable maximum but your mileage may vary. If you have existing networks; you can freeze them and use either of the methods below, but I occasionally see the script throw up false positives under these circumstances.

Select unfrozen

If checked, use the first option described above. For the purposes of this script it doesn't matter if the backbone or side chain is frozen.

Mutate segments

Relevant iff Select unfrozen above is not selected (I find this the more useful way of doing things). List the residues to mutate (ranges are allowed) separated by commas in a way already used by many other scripts; e.g. 34,36,41-44, etc.

Amino acids

The list of possible replacements. All amino acids that contain a donor or acceptor are included; however it might be wise to prune this list a bit depending on circumstances: for example if you are looking for networks in the core of the complex you might want to omit lysine (k) and arginine (r). While you may well get more networks the hiding and sidechain score penalties will likely to be too great to make them worthwhile.

Filter threshold

Of questionable utility: this can probably be ignored. Only gains in the HNet filter greater than this value will be recorded.

The script chugs away: any networks found will be saved in quicksave slots (13+) and a suitable message printed out in the Recipe Output window. It's recommended that you kill the script when you've got a few networks and take a look (enable all the filters; show networks; freeze the residues that make up the network; mutate and wiggle)