Recipe: UnBUN_1.0

created by mwm64

Profile

• Name: UnBUN_1.0
• ID: 103681
• Shared with: Public
• Parent: None
• Children: None
• Created on: July 07, 2020 at 00:44 AM UTC
• Updated on: July 07, 2020 at 00:44 AM UTC
• Description:

  Script that tries to make bonds to the target protein and reduce BUNS.

Code

-- unbun
-- Try to get rid of  BUNS by finding hydrophilic segments in the
-- target protein  that are near segments in the user protein
-- and mutating the user protein segment  to something that can 
-- bond with that target; keeping changes that improve our BUN
-- score

iterations=2
bond_radius=7
keepbands=false

print("unbun: starting with iterations=" .. iterations .. " and bond_radius=" .. bond_radius )

function GetBondableAcids(acid)
    -- if this is a "red" acid, return the list of blue ones
    -- and vice versa; if its a red-blue one return both
    -- and if its a M, return the same...
    if acid == 'k' or acid == 'r' or acid == 'h' or acid == 'w' then
        return {'e','d','s','t','y'}
    end
    if acid == 'e' or acid== 'd' or acid =='s' or acid == 't' or acid == 'y' then
        return {'k','r','h','w'}
    end
    if acid == 'm' then
        return {'m'}
    end
    -- otherwise pretend its a red-blue, and try lots..
    return {'k','r','h','w','e','d','s','t','y'}
end

-- first find the BUN filter so we can check for improvement
--
satfilt = -1
filt = filter.GetNames ()
print ( #filt .. " conditions or filters" )
for ii = 1, #filt do
    print( "checking filter " .. ii .. ": " .. filt[ii] )
    if string.match(filt[ii],".*sat") then
        print( "found sat filter " )
        satfilt = ii
    end
end


-- pick a radius of how close two segments need to be to form
-- bond...

recipe.SectionStart("unbun")
recipe.ReportStatus()
undo.SetUndo(false)
if satfilt >= 0 then
    nsegs = structure.GetCount()
    -- guess that the boundary between target and user segments is halfway
    boundary = math.floor( nsegs/2 )
    orig_nsat_bonus = filter.GetBonus(filt[satfilt])
    for tps = 1, boundary do
        if not structure.IsHydrophobic(tps) then
            -- look up amino acids to try against this protein
            taa = structure.GetAminoAcid(tps)
            bonding_acids = GetBondableAcids(taa)
            print("got for acid " .. taa .. " list " .. table.concat( bonding_acids,","))
            recipe.SectionStart("mutate_candidate")
            recipe.ReportStatus()
            for ups = boundary, nsegs do
                if structure.IsMutable(ups) and structure.GetDistance(tps, ups) < bond_radius and string.len(structure.GetAminoAcid(ups)) == 1 then
                    print("Trying to bond segment " .. ups .. " to " .. tps)
                    -- keep max bonus and corresponding protein
                    -- max (so far) is where we are now
                    max_nsat_bonus = filter.GetBonus(filt[satfilt])
                    maxbonusacid = structure.GetAminoAcid(ups)
                    recentbest.Save()
                    print("got amino acid " .. maxbonusacid)
                    selection.DeselectAll()
                    selection.Select(ups)
                   
                    for bai = 1,#bonding_acids do
                        print("A setting " .. ups .. " to " .. bonding_acids[bai])
                        structure.SetAminoAcid(ups, bonding_acids[bai])
                        -- sometimes just mutating it adds a bond, so skip shake and or wiggle if
                        -- the score is already better...
                        bonus = filter.GetBonus(filt[satfilt])
                        if bonus <= max_nsat_bonus then
                            -- maybe if we shake it it will bond?
                            structure.ShakeSidechainsSelected(iterations)
                            bonus = filter.GetBonus(filt[satfilt])
                        end
                        if bonus <= max_nsat_bonus then
                            --  see if wiggling with the band will bond it...
                            -- try to band the sidechains so wiggle will try to make the bond
                            tcount = structure.GetAtomCount(tps)
                            ucount = structure.GetAtomCount(ups)
                            myband = band.AddBetweenSegments(tps, ups, tcount, ucount)
                            band.SetGoalLength(myband,1.5)
                            band.SetStrength(myband, 1.5)
                            structure.WiggleAll(iterations)
                            band.Delete(myband)

                            bonus = filter.GetBonus(filt[satfilt])
                        end

                        if bonus < max_nsat_bonus then
                            -- tweaking this broke a BUNS bond, 
                            -- (without adding others)
                            -- put it back and give up on this
                            -- target segment...
                            recentbest.Restore()
                            break
                        end
                        if bonus > max_nsat_bonus then
                            -- we have a new winner!!!
                            maxbonusacid = bonding_acids[ bai]
                            max_nsat_bonus = bonus
                            recentbest.Save()
                            print("new best: " .. bai .. " gets ".. bonus)
                        else
                            -- our bonus is equal, but... 
                            -- we probably broke the overall score, 
                            -- so put it back
                            recentbest.Restore()
                        end
                    end
                    recipe.ReportStatus()
                end
            end
            recipe.SectionEnd()
        end
    end

else
    print( "Couldn't find sat filter, quitting" )
end
undo.SetUndo(true)
recipe.SectionEnd()

Comments

[mwm64]

You went in by hand, in design mode, and hooked up your protein to the target protein, in like a dozen places, and then you Wiggled, or Mutated, and it ripped out your bonds, and attached them back to the protein… This is the tool that will put the bonds back on to the target protein, and even add a few that you missed.

Hopefully this will help more folks get proteins that bond next time…