# YASARA MACRO

# TOPIC: 5. Structure prediction

# TITLE: Showing the docking results interactively
# REQUIRES: Structure
# AUTHOR: Elmar Krieger
# LICENSE: GPL
# DESCRIPTION: This macro provides an interactive player to cycle through the
docking poses and clusters

# You can either set the target structure by clicking on Options > Macro > Set
target,
# by providing it as command line argument (see docs at Essentials > The command
line),
# or by uncommenting the line below and specifying it directly.
#MacroTarget='/home/myname/projects/docking/1sdf'

# Set playback waittime (1 is maximum playback speed)

waittime=12

# Flags of interactions to show by default (combined with |):

# 1=H-Bonds, 2=Hydrophobic, 4=Pi-Pi, 8=Cation-Pi, 16=Ionic
intflags=1|2|16

# Normally no change required below this point

# ============================================

# Sanity checks
if MacroTarget==''
RaiseError "This macro requires a target. Either edit the macro file or click
Options > Macro > Set target to choose a target structure"

Console off

intnamelist='Hydrophobic','PiPi','CationPi','Ionic'

# PART 1 - DOCKING POSE ANALYSIS

DockingPoses:

# Load the result scene

Clear
scefilename='(MacroTarget).sce'
scene = FileSize (scefilename)
if not scene
# No scene present, presumable dock_runensemble was used with scesaved=0, proceed
to cluster playback.
receptors=999
Go DockingClusters
LoadSce (scefilename)

# Determine if this was a single receptor&ligand, a receptor ensemble, or a virtual

screening
receptorlist() = ListObj Receptor???
receptors = count receptorlist
ligandlist() = ListObj Ligand????
ligands = count ligandlist
if !receptors
RaiseError 'No receptor object with name Receptor... was found, please make sure
to run the dock_run macro first'
if ligands
 receptorruns = CountMol Obj (ligandlist1)
# Collect all ligand energies
for i=1 to ligands
for j=001 to receptorruns
if j<1000
seg='C(j)'
else
seg=j
bindnrg = BFactorAtom Obj Ligand(i) Segment (seg)
# Create a list of info strings for each run: -binding energy, ligand number,
and segment ID
runinfolist((i-1)*receptorruns+j)='(-bindnrg) (i) (seg)'
if receptors>1
# If there is more than one receptor (dock_runensemble), then there is just one
ligand
ligands=1
runs=receptors*receptorruns*ligands
else
# Covalent docking doesn't have a ligand object
if receptors>1
RaiseError 'Only one receptor expected for covalent docking'
receptorruns = CountMol Segment C??? Obj RecepFlex
for i=1 to receptorruns
seg='C(000+i)'
bindnrg = BFactorAtom Obj RecepFlex Segment (seg)
# Create a list of info strings for each run: -binding energy, ligand number,
and segment ID
runinfolist(i)='(-bindnrg) (i) (seg)'
runs=receptorruns
# Sort the info strings using the reversed binding energy (best binders first)
runinfolist()=sort runinfolist
if runs!=count runinfolist
RaiseError 'Number of runs differ [(runs) and (count runinfolist)], please
contact support'

# Create the user interface

ShowPlayer 'Pose'
run=0
step=1
delay=waittime
mainloop='PoseMainLoop'

# Loop through the docking poses

PoseMainLoop:
while 1
if run<0 or run>=runs
Go RewindToStart
# Determine docking cycle (receptor ensemble member or virtual screening ligand)
# and segment names for current run
_,cycle,seg=split runinfolist(run+1)
if receptors>1
# Receptor ensemble
recobj='Receptor(cycle)'
flxobj='RecFlex(cycle)'
ligobj='Ligand(cycle)'
elif ligands>1
# Virtual screening
recobj='Receptor'
flxobj='RecFlex(cycle)'
 ligobj='Ligand(cycle)'
elif ligands
# Normal docking
recobj='Receptor'
flxobj='RecFlex'
ligobj='Ligand'
else
# Covalent docking
recobj='Receptor'
flxobj='RecepFlex'
ligobj=flxobj
flexobjects = CountObj (flxobj)
if !flexobjects
# No flexible receptor part, try RecepFlex instead of RecFlex (needed for
screening)
_,_,_,chrlist() = crack flxobj
flxobj='Recep'+fuse chrlist
# Show the corresponding receptor and ligand
SwitchObj !SimCell,off
SwitchObj (recobj) (flxobj) (ligobj),On
HideObj (flxobj) (ligobj)
HideSecStrObj (flxobj) (ligobj)
ShowAtom Segment (seg) Obj (flxobj) (ligobj)
ShowSecStrRes Segment (seg) Obj (flxobj) (ligobj)
# Always hide the flexible side-chains in the receptor
fixedatoms = CountAtom fixed Obj (recobj)
if fixedatoms
# Get a list of partly free residues in recobj
reslist() = ListRes !fixed Obj (recobj)
# Show their sidechains
ShowAtom SCwithBB Res (join reslist) Obj (recobj)
# And hide whatever is not fixed (to show RecepFlex atoms instead)
HideAtom !fixed Obj (recobj)
# For covalent docking, there may be free backbone atoms, don't show secondary
structure there
HideSecStrRes !fixed Backbone Obj (recobj)
# Change the marked atoms in ligand and flexible sidechains to the currently
visible ones
atomlist() = MarkAtom
for i=1 to 4
atom = ListAtom (atomlist(i)),Format='ATOMNAME Res RESNAME RESNUM Mol MOLNAME
Obj OBJNUM visible'
atomlist(i) = ListAtom (atom)
MarkAtom (atomlist),Zoom=1
# Update the player
UpdatePlayer run,runs,'Segment (seg) Obj (ligobj)'
# Proceed to next pose
run=run+step
if step
# Wait a bit
Wait (delay)
else
# Pause mode, wait until next click
Wait forever

# PART 2 - DOCKING CLUSTER ANALYSIS

DockingClusters:
Clear
# Determine cluster format
for format in 'yob','pdb'
exists = FileSize (MacroTarget)_001.(format)
if exists
break
# Count the clusters
for runs=000 to 9999
exists = FileSize (MacroTarget)_(runs+1).(format)
if !exists
break
if runs<1
RaiseError "No docking clusters have been found. This macro must be applied to a
docking project created with one of the 'dock_run*' macros"
# Create the user interface
ShowPlayer 'Cluster'
run=0
step=1
delay=waittime
posorilist=0,0,50,0,0,0
mainloop='ClusterMainLoop'

# Loop through the docking clusters

ClusterMainLoop:
while 1
DelObj (join intnamelist)
if run<0 or run>=runs
Go RewindToStart
obj = Load(format) (MacroTarget)_(001+run)
# Remove line below to display ligand names for screening runs made with YASARA
versions < 15.10
UnlabelAll
CenterAtom CA Obj (obj)
if Objects==1
Pos 0,0,50
Style Ribbon,Stick
BallRes Segment C???
else
TransferObj 2,1,Local=Keep
CopyStyleObj 1,2
SwapObj 1,2
DelObj 2
FreeAll
# Show the various interactions
if intflags&1
ShowHBoAtom Segment C???,Extend=Yes
else
HideHBoAll
for i=1 to count intnamelist
if intflags&(1<<i)
ShowIntAtom Segment C???,Segment !C???,Type=(intnamelist(i)),Occluded=No
ColorAll Element
# Update the player
# The ligand is selected via the last atom in the soup */
UpdatePlayer run,runs,'Atom (atoms)'
# Proceed to next pose
run=run+step
if step
# Wait a bit
Wait (delay)
else
 # Pause mode, wait until next click
Wait forever

# CREATE PLAYER USER INTERFACE

# ============================
# 'type' is 'Pose' or 'Cluster'
def ShowPlayer type
global gpos,intflags,ligands

PrintHUD
FillRect
Font Arial,Height=20,Color=White
PosText X=160,Y=8,Justify=Center
Print 'Docking (type) Player'
FillRect X=15,Y=30,Width=290,Height=1,Color=White
Font Height=14,Spacing=1.3
PosText X=25,Y=46,Justify=Left
if type=='Pose'
Print 'Docking run:\n'
else
Print 'Cluster:\n'
Print 'Binding energy:\nDiss.constant:\nLigand:'
# Create the clickable color gradient on the right.
# Its position 'gpos' is made global, so that it can be used by function
UpdatePlayer
Font MonoSpaced,Spacing=1
gpos=240,135
FillRect (gpos1),(gpos2+5),Width=32,Height=241,Color=White
for i=0 to 10
PosText (gpos1/8+6),(gpos2/12+i*2+1),Justify=Left
Print '(i*10)%'
FillRect (gpos1+32),(gpos2+i*24+5),Width=8,Height=1,Color=White
# Top and bottom button have half the height
if !i
y=gpos2+6
h=12
else
y=gpos2+i*24-7
h=24-12*(i==10)
ShowButton X=(gpos1+16),Y=(y),Width=30,Height=(h),Border=0,
Color=(i*320/11),Action='Go ClickGradient,GoPar=(i)'
PosText (gpos1/8+3),(gpos2/12+22),Justify=Center
Print 'Click'
PosText (gpos1/8+3),(gpos2/12+23),Justify=Center
Print 'above'
# Create the buttons
Font Arial,Height=14,Spacing=1.3
ShowButton 'Play',X=70,Y=(gpos2)
ShowButton 'Pause',X=160,Y=(gpos2)
ShowButton 'Step backward',X=120,Y=(gpos2+50)
ShowButton 'Step forward',X=120,Y=(gpos2+100)
ShowButton 'Fast forward',X=120,Y=(gpos2+150)
ShowButton 'Rewind to start',X=120,Y=(gpos2+200)
if type=='Pose'
if ligands
# We cannot save poses during covalent docking, because the flexible part is
in a different object
PosText X=0,Y=(gpos2+260)
 Print 'Save pose:'
ShowButton 'PDB',X=130,Y=(gpos2+250)
ShowButton 'YOb',X=190,Y=(gpos2+250)
ShowButton 'Proceed to cluster
analysis',X=174,Y=(gpos2+300),Color=404040,Action='Go DockingClusters'
else
# Show the interaction buttons to toggle
namelist='H-Bonds','Hydrophobic','Pi/Pi','+/Pi','Ionic'
poslist=40,130,205,248,294
for i=1 to count namelist
if intflags&(1<<(i-1))
buttoncol='808080'
fontcol='White'
else
buttoncol='303030'
fontcol='Black'
Font Height=11,Color=(fontcol),Spacing=1.3
ShowButton (namelist(i)),X=(poslist(i)),Y=(gpos2+320),Color=(buttoncol)
Font Arial,Height=14,Color=White,Spacing=1.3
PosText X=160,Y=(gpos2+300),Justify=Center
Print 'Select interactions to show:'
ShowButton 'Return to all poses',X=120,Y=(gpos2+250),Color=404040,Action='Go
DockingPoses'

# UPDATE PLAYER USER INTERFACE

# ============================
def UpdatePlayer run,runs,ligandsel
global gpos

# The atomic B-factor contains the free binding energy in kcal/mol (positive is
better).
bindnrg = BFactorAtom (ligandsel)
# The atomic property contains the picomolar [pM] dissociation constant.
dissconst = PropAtom (ligandsel)
if bindnrg<=0
dissconst='None'
elif dissconst>=100000000
dissconst='Gigantic'
elif dissconst>=100000
dissconst=0+dissconst
else
dissconst=0.000+dissconst
# Display run, binding energy and dissociation constant
FillRect X=170,Y=44,Width=150,Height=70
PosText X=170,Y=46,Justify=Left
Print '(1+run)/(0+runs)\n(0.00+bindnrg) kcal/mol\n(dissconst) pM'
# Display first 20 characters of ligand name (compound)
FillRect X=100,Y=115,Width=220,Height=18
compound = CompoundMol (ligandsel)
if compound==''
compound='unnamed'
compound()=crack compound
PosText X=100,Y=115,Justify=Left
len=count compound
# Maximum reached with uppercase ALCOHOL DEHYDROGENASE
if len>15
len=15
for i=1 to len
Print '(compound(i))'
 if runs>1
# Show the '>' at the color gradient
FillRect X=(gpos1-20),Y=(gpos2),Width=15,Height=260
PosText X=(gpos1-20),Y=(gpos2+240*run/(runs-1))
Print '>'

# HANDLE THE PLAYER BUTTONS

# =========================

# Press the Play button

Play:
step=1
delay=waittime
Go (mainloop)

# Press the Pause button

Pause:
step=0
delay=waittime
Go (mainloop)

# Press the step forward button

StepForward:
run=run+1
Go (mainloop)

# Press the step backward button

StepBackward:
run=run-1
Go (mainloop)

# Press the fast forward button

FastForward:
step=1
delay=1
Go (mainloop)

# Press the rewind to start button

RewindToStart:
run=0
if step<0
Go Play
Go (mainloop)

# Click the color gradient on the right

ClickGradient:
run=(runs-1)*GoPar/10
Go (mainloop)

# Save a pose in PDB format

PDB: format='pdb'
Go SavePose

# Save a pose in YOb format

YOb: format='yob'

SavePose:
# Ask for PDB/YOb filename to save
_,filename = ShowWin Type=FileSelection,Title='Choose filename to save current
complex in (format) format',
MultipleSelections=No,Filename='*.(format)'
# Duplicate the receptor ligand objects
objlist() = DuplicateObj (recobj) (ligobj)
# Keep only the current ligand pose
DelAtom Segment !(seg) Obj (objlist2)
# Transfer atom coordinates of flexible residues to receptor
reslist() = ListRes Obj (flxobj),Format='RESNAME RESNUM Mol MOLNAME'
for res in reslist
# Get atom names in PDB3 format, so that equivalent hydrogens are numbered
atomlist() = ListAtom Res (res) Segment (seg) Obj (flxobj)
namelist() = ListAtom (join atomlist),Format='ATOMNAMEPDB3'
poslist() = PosAtom (join atomlist)
for i=1 to count atomlist
PosAtom PDB3 (namelist(i)) Res (res) Obj (objlist1),(poslist(i*3-2)),
(poslist(i*3-1)),(poslist(i*3))
# Recreate aliphatic hydrogens of flexible residues in receptor, docking doesn't
yield coordinates for them
DelAtom Element H Res (res) Obj (objlist1) with bond to Element C
AddHydRes (res) Obj (objlist1),Update=No
# Join to single object and add aliphatic hydrogens again
JoinObj (objlist2),(objlist1)
FreeObj (objlist1)
# Save and delete
Save(format) (objlist1),(filename)
DelObj (objlist1)
Go (mainloop)

# Toggle the interactions during cluster visualization

# Hydrogen bonds
HBonds:
intflags=intflags^1
ShowPlayer 'Cluster'
Go (mainloop)

# Hydrophobic interactions
Hydrophobic:
intflags=intflags^2
ShowPlayer 'Cluster'
Go (mainloop)

# Pi/Pi interactions
PiPi:
intflags=intflags^4
ShowPlayer 'Cluster'
Go (mainloop)

# Cation/Pi interactions
CationPi:
intflags=intflags^8
ShowPlayer 'Cluster'
Go (mainloop)

# Ionic interactions
Ionic:
intflags=intflags^16
ShowPlayer 'Cluster'
Go (mainloop)