Recipe: Ligand_Optimize_v2

created by Fasodankfds

Profile

• Name: Ligand_Optimize_v2
• ID: 109350
• Shared with: Public
• Parent: Ligand_Optimize_v1
• Children:
  • Ligand_Optimize_v2.1
• Created on: February 03, 2026 at 06:52 AM UTC
• Updated on: February 03, 2026 at 06:54 AM UTC

Code

--[[
Ligand Binding Pocket Optimizer v1.0
Optimizes protein residues around ligands by:
- Finding residues near ligands
- Testing different amino acid types (if mutable)
- Testing rotamers for nearby residues

- V2
    Expanded search range
    Expanded wiggle range
]]--

local CONFIG = {
    SEARCH_RADIUS = 8.0,  -- Angstroms around ligand
    WIGGLE_ITERATIONS = 15,
    MUTATE_ITERATIONS = 2,
    BEST_SLOT = 8
}

function getScore()
    return current.GetEnergyScore()
end

function findLigands()
    local ligands = {}
    for i = 1, structure.GetCount() do
        if structure.GetSecondaryStructure(i) == "M" then
            table.insert(ligands, i)
        end
    end
    return ligands
end

function findNearbyResidues(ligandSeg, radius)
    local nearby = {}
    local totalSegs = structure.GetCount()
    
    for seg = 1, totalSegs do
        if structure.GetSecondaryStructure(seg) ~= "M" then
            local dist = structure.GetDistance(ligandSeg, seg)
            if dist < radius then
                table.insert(nearby, {seg = seg, dist = dist})
            end
        end
    end
    
    table.sort(nearby, function(a, b) return a.dist < b.dist end)
    return nearby
end

function optimizeRotamers(segments)
    local improvements = 0
    save.Quicksave(CONFIG.BEST_SLOT)
    local bestScore = getScore()
    
    for _, segData in ipairs(segments) do
        local seg = segData.seg
        local rotCount = rotamer.GetCount(seg)
        
        if rotCount > 1 then
            for rotIdx = 1, rotCount do
                rotamer.SetRotamer(seg, rotIdx)
                structure.ShakeSidechainsAll(1)
                structure.WiggleAll(CONFIG.WIGGLE_ITERATIONS)
                
                if getScore() > bestScore then
                    bestScore = getScore()
                    improvements = improvements + 1
                    save.Quicksave(CONFIG.BEST_SLOT)
                    print(string.format("Seg %d rot %d: %.3f", seg, rotIdx, bestScore))
                else
                    save.Quickload(CONFIG.BEST_SLOT)
                end
            end
        end
    end
    
    return improvements
end

function mutatePocket(segments)
    local hasMutables = false
    
    -- Check if any are mutable
    for _, segData in ipairs(segments) do
        if structure.IsMutable(segData.seg) then
            hasMutables = true
            break
        end
    end
    
    if not hasMutables then
        print("No mutable residues in binding pocket")
        return 0
    end
    
    local startScore = getScore()
    save.Quicksave(CONFIG.BEST_SLOT)
    
    selection.DeselectAll()
    for _, segData in ipairs(segments) do
        if structure.IsMutable(segData.seg) then
            selection.Select(segData.seg)
        end
    end
    
    structure.MutateSidechainsSelected(CONFIG.MUTATE_ITERATIONS)
    structure.WiggleAll(CONFIG.WIGGLE_ITERATIONS)
    
    local gain = getScore() - startScore
    if gain > 0 then
        save.Quicksave(CONFIG.BEST_SLOT)
        print(string.format("Mutation gain: +%.3f", gain))
        return 1
    else
        save.Quickload(CONFIG.BEST_SLOT)
        return 0
    end
end

function optimizeLigandPocket()
    local ligands = findLigands()
    
    if #ligands == 0 then
        print("No ligands found")
        return
    end
    
    print(string.format("Found %d ligand(s)", #ligands))
    local startScore = getScore()
    print(string.format("Starting score: %.3f", startScore))
    
    for _, ligandSeg in ipairs(ligands) do
        print(string.format("\nOptimizing pocket around ligand %d", ligandSeg))
        
        local nearby = findNearbyResidues(ligandSeg, CONFIG.SEARCH_RADIUS)
        print(string.format("Found %d residues within %.1fÅ", #nearby, CONFIG.SEARCH_RADIUS))
        
        -- Show nearby residues
        if #nearby > 0 then
            local segList = {}
            for i = 1, math.min(10, #nearby) do
                table.insert(segList, nearby[i].seg)
            end
            print("Closest: " .. table.concat(segList, ", "))
        end
        
        -- Try mutations if available
        mutatePocket(nearby)
        
        -- Optimize rotamers
        local improvements = optimizeRotamers(nearby)
        print(string.format("Rotamer improvements: %d", improvements))
    end
    
    -- Final polish
    print("\nFinal wiggle...")
    structure.WiggleAll(CONFIG.WIGGLE_ITERATIONS * 2)
    
    local finalScore = getScore()
    local totalGain = finalScore - startScore
    
    print(string.format("\n=== Results ==="))
    print(string.format("Start:  %.3f", startScore))
    print(string.format("Final:  %.3f", finalScore))
    print(string.format("Gain:   %.3f", totalGain))
    
    save.Quicksave(3)
end

function requestSettings()
    local ask = dialog.CreateDialog("Ligand Pocket Optimizer")
    
    ask.radius = dialog.AddSlider("Search Radius (Å)", 
        CONFIG.SEARCH_RADIUS, 1, 5000, 1)
    ask.wiggle = dialog.AddSlider("Wiggle Iterations", 
        CONFIG.WIGGLE_ITERATIONS, 1, 10000, 0)
    
    ask.OK = dialog.AddButton("Start", 1)
    ask.Cancel = dialog.AddButton("Cancel", 0)
    
    if dialog.Show(ask) > 0 then
        CONFIG.SEARCH_RADIUS = ask.radius.value
        CONFIG.WIGGLE_ITERATIONS = ask.wiggle.value
        return true
    end
    return false
end

function main()
    if not requestSettings() then
        print("Cancelled")
        return
    end
    
    behavior.SetClashImportance(1)
    save.Quicksave(1)
    optimizeLigandPocket()
end

function cleanup(err)
    print("Error: " .. tostring(err))
    save.Quickload(1)
end

xpcall(main, cleanup)