1. Maestro environment in practice Balázs Jójárt

2. Today …  how to draw a small molecule && make nice pictures  how to handla large molecule, like a protein, which contain several tens of amino acids

3. Draw a small molecule – ephedrine I.  make a directory on your laptop: SS2015  inside that directory  0.maestro  launch Maestro  View  Workspace  Display Atoms  Representation  Build  Fragments  Project/Change Directory…  set it to SS2015/0.maestro  this will our working directory

4. Draw a small molecule – ephedrine II.  let’s start with drawing ;)  click on phenyl ring on the right hand side && click into the workspace  middle button click  rotate  right button click  translate  middle button scroll  scale  use the ‚pencil’ button to draw 3 single bonds  make an additional bond for OH and one other for methyl group  click on „hydroxyl” and click on the appropriate position  click on „planar amine” and click on the appropriate position

5. Draw a small molecule – ephedrine III.  change the hydrogen (located in the chain) to C: Set Element  add missing hydrogens: Edit/Add Hydrogens/All  cleaning up geometry: local geometry optimization  check chirality: (1R,2S)-2-(methylamino)-1-phenylpropan-1-ol  Edit/Adjust/Chirality and click Label Chiral Centers  if not good  R   S && Clean up geometry  change the protonation state of ephedrine  increase the charge to +1 for N  Edit/Add Hydrogens/All  cleaning up geometry

6. Create a project file  structure is presented only in the workplace  if we close Maestro it will be lost  solution:  we save a project file, which contains everything (color, drawing method, orientation etc.)  Project/Save as…  epehdrine.epinephrine.norepinephrine.prj  Ctrl+W  closing the project  Ctrl+O  open a project  change the orientation of the molecule (middle button click)  Ctrl+W and Ctrl+O  if the structure is not in the centre   change the name of the mol  left hand site, Title, double click, ephedrine & enter

7. Export an image  representation  small triangles / All  View/3D Options…  Backgrounds: white, for printing always !!!!!!! or tansparent bg  Lightening: turn on/off second light  Materials: Rubber  click on  use ‘Options’  transparent bg - optionally  use ‘tif’ format  DPI  colour figs: at least 300 (max 600)  black & white : at least 600 (max 1200)  save to ephedrine.tif ~ 60 Mb  save to ephedrine.png ~ smaller 320 Kb up to you

8. Continue with epinephrine & nor~ I.  we will use this structure to generate the remaining molecules  BUT: if we change the structure  change the project file  not a good idea ;)  Right click on ephedrine (entry list)  Duplicate/In Place  change the name to epinephrine  we have to include two OH groups  we have to remove a CH3 group: click on Hs and the C  add missing hydrogens: Edit/Add Hydrogens/All  cleaning up geometry: local geometry optimization  save to epinephrine.png

9. Continue with epinephrine & nor~ II.  we have to delete only the terminal CH3 group  steps:  duplicate  change the name  use  add missing Hs  use  save to norepinephrine.png PLAY @ HOME with this feature

10. Playing with protein structures  target molecule: beta2- adrenerg receptor  sequence:  MGQPGNGSAFLLAPNGSHAPDHDVTQERDEVWVVGMGIVMSLIVLAIVFGNVLVITAIA KFERLQTVTNYFITSLACADLVMGLAVVPFGAAHILMKMWTFGNFWCEFWTSIDVLCVT ASIETLCVIAVDRYFAITSPFKYQSLLTKNKARVIILMVWIVSGLTSFLPIQMHWYRATHQE AINCYANETCCDFFTNQAYAIASSIVSFYVPLVIMVFVYSRVFQEAKRQLQKIDKSEGRF HVQNLSQVEQDGRTGHGLRRSSKFCLKEHKALKTLGIIMGTFTLCWLPFFIVNIVHVIQD NLIRKEVYILLNWIGYVNSGFNPLIYCRSPDFRIAFQELLCLRRSSLKAYGNGYSSNGNT GEQSGYHVEQEKENKLLCEDLPGTEDFVGHQGTVPSDNIDSQGRNCSTNDSLL  what is the 3D structure? ;)  go to www.rcsb.orgwww.rcsb.org  every structure has a 4 letter code: 3sn6

11. 3sn6 I.  Project  Get PDB  3sn6  chain R: only chain R is included  create groups  right click on 3SN6  Group/New.. & enter receptor  select 3 ligands  right click, Group/New.. & ligands

12. 3sn6 II.  rotate the molecule as on the figure  we will not consider one part of the molecule  delete it & Fit to Workspace  Show Ribbons for All residues  hide protein atoms: click and select protein  display only amino acids nearby the ligand atom  PLAY a little bit with this structure & save a good figure about it

13. Into report from Ligprep  figures:  about molecules  about the receptor