Note: 

• Due date: Same Day.

• Get Molecule files:

• These files are stored on a special hard disk. You can get them by means of the following steps:
• Open UNIX shell window through Desktop (on Toolchest) => Open Unix Shell.
• Type in UNIX command: " cp /disk2/local/biochem/molecule/* . "

• 3D graphics of a protein:

• Type in UNIX command: " sybyl"
• Load a protein:
• File=>Read=>(select protein.pdb)=>OK=>YES.
• Display the protein in Ribbon representation:
• Biopolymer=>Display=>Shaded Ribbon=>All=>OK.
• Highlight active residues ASP29 and ASP30 by spacefill representation:
• View=>Mixed Rendering=>(select spacefill)=>OK=>Substructures=>(select ASP29, ASP30)=>OK=>OK.
• Print the graphics:
• Type your name(s) in SYBYL window: View=>Annotation=>A=>(click a site) => type your name in
• File=>Print=>Screen Capture Output=>Create=>Imgview=>(select imgfil.rgb)=>OK
• In ImageView Window: File=>Print
• Close Imageview and Image windows.
• Delete the protein:
• Build/Edit=>Zap (delete) Molecule.
 
 
 
• Molecular modeling of a drug

• Load a drug:
• File=>Read=>(select ligand.pdb)=>OK=>YES.
• Add hydrogens to this drug:
• Build/Edit=>Add=>Hydrogens
• Load charges to this drug:
• Compute=>Charges=>Gaisteiger-Huckel=>No
 
•  Conduct molecular mechanics computation to find lowest potential energy conformation for this drug:

• Use Compute=>Minimize to conduct molecular mechanics computation.
• Use the following parameters:
• Max Iterations: 1000
• Leave the rest of parameters as default.
• Print out the minimized 3D structure by the following procedure:
• Type your name(s) in SYBYL window
• File=>Print=>Plotter/Printer Output=>Picture Type: Ball & Stick=>Print=>Xpsview=> (select file: pltfil.eps)
 
 
• Determine molecular surface of this drug by the following procedures:
• View=>Molcad Surfaces=>molecular surface => Create=>Type:Connolly.
• Explore difference representation modes. You can generate very cool pictures for this drug!
• Delete this drug.
 
 

• Ligand-protein docking by using SYBYL

• Load protein (protein.pdb) and ligand (ligand.pdb). It is recommended that protein be loaded first.
• Start docking by the following procedures:
• Biopolymer=>Flexidock=>Create An Input File=>OK
• Close the No Pocket Defined window.
• In Protein Display Options window, click Define Pocket.
• In Atom Expression window:
• Replace M1(0) with M1(957)
• Click OK.
• In Protein Display Options window, increase the radius to 10.
• In Set Up Flexidock window, go through the check list to
• remove water
• add hydrogens and charges
• choose rotatable bonds (use: Add=>All=>OK)
• mark H-bond sites (use Add=>All=>OK on every item in Defining H-bond Sites window)
• Provide a file name, then click on Write Out Flexidock ... and Flexidock It sequentially..
• Print the graphics:
• Type your name(s) in SYBYL window: View=>Annotation=>A=>(click a site).

File=>Print=>Screen Capture Output=>Imgworks=>(select imgfil.rgb)=>OK
In Image View Window: File=>Print
 
 
 
•  Ligand-protein docking by using INVDOCK

Open UNIX shell window through Desktop (on Toolchest) => Open Unix Shell.

Pre-processing the ligand profile by typing the following commands in the Shell window:
 

Type command "/disk2/local/biochem/prog/convtpdb"

Check whether three files prefixed with "ligand2" have been generated by using command "ls".

Type command "/disk2/local/biochem/prog/spreligand"

Check whether two files prefixed with "ligand3" have been generated.
 

Run DOCKSM program of INVDOCK to dock the ligand onto the cavity of protein:

Type command "/disk2/local/biochem/prog/docksm" . The running time is about 10-20 minutes. Be patient! The running time of SYBYL docking program is much longer.

Check whether the files prefixed with "1hvi000" have been generated.
 
 

Analyze the binding energy between docked ligand and host protein.

Using the command: "/disk2/local/biochem/prog/checkrank".

Check if the file "ranklist" has been generated and use "nedit" to view it. (Command is "nedit  ranklist".)

Add your name at the bottom of this file and print it: File=>Print.
Exit nedit: File=>Exit.

View the docking result:

        Reopen SYBYL.
        Load the protein:
           File=>Read=>(select protein.pdb)=>OK=>NO.
        Load the docked ligand:
           File=> Read=>(select 1hvi0000101.pdb)=> OK => NO.
        Display the protein in Ribbon representation:

 Biopolymer=>Display=>Shaded Ribbon=>All=>OK.

        Highlight the drug by spacefill representation:

  View=>Mixed Rendering=>(select spacefill)=>OK=>(select "M2: <no name>")=>Substructure=>(select A77800)=>OK=>OK.

 

Print the graphics:
 

Same steps as given above.

You can also have a look at other binding configurations generated by INVDOCK. They are in 1hvi0000102.pdb 1hvi0000103.pdb etc. separately. You can load them in the same way.