Amber: How to set-up calculations

1. Amber: How to set-up calculations

2. Preliminary Remarks • Amber is a very sophisticated piece of scientific software and as such requires some amount of time to learn it. • Although Amber may appear very complex at first, it is reasonably straightforward once you understand the basic architecture and option choices. • The best source of help for active users of the Amber software is the amber mailing list and the mailing list archive (http://amber.scripps.edu). Questions sent to this list will go to all active amber uses and so you get the help of the amber community.

3. Preliminary Remarks • Have a look at the Amber Home Page: http://amber.scripps.edu

4. Preliminary Remarks:Importance of Visualization • One quick look at the structure can help to detect errors and save days or weeks of your time

5. Importance of Visualization: Real Life Example A person spent many days trying to minimize a structure using Gaussian… It was no success… One quick look immediately discovered a problem Problem

6. Importance of Visualization: Real Life Example A person spent many days running Molecular Dynamics using Amber… He was experiencing crashes of Amber during his runs … Visual inspection of his molecular structures showed that initial structures had had not well prepared. Oxygen atom is missing Incomplete valencies on atoms… Hydrogen atom is missing The structure also had a steric clash between two amino acid residues which could lead to a program overflow error

7. Freeware Visualization Programs:RasMol http://www.openrasmol.org/

8. Freeware Visualization Programs:VMD http://www.ks.uiuc.edu/Research/vmd/

9. Freeware Visualization Programs:gOpenMol http://www.csc.fi/gopenmol/

10. http://sirius.sdsc.edu/

11. Freeware Visualization Programs:Chimera http://www.cgl.ucsf.edu/chimera/

12. Freeware Visualization Programs:JMolEditor It is a Java program, i.e. it is cross-platform We plan to add support for all Amber and Gaussian input and output files http://sf.anu.edu.au/~vvv900/cct/appl/jmoleditor/index.html

13. If you are really serious about Biomolecular Simulations… • … you will need an expert molecular modeling environment which provides construction, editing, and visualization tools for both large and small molecules • Tripos (www.tripos.com) • Accelrys (http://www.accelrys.com) • and others…

14. Amber Basic Tutorials • Amber distribution CD comes with several basic tutorials(under amber9/tutorial): Additional tutorial examples are available at http://amber.scripps.edu.

15. Basic Steps for Running Simulation • Obtain starting Coordinates (PDB, NMR, Database, Program generated) • Run LEaP to generate the parameter and topology file. • Run Simulation (sander or pmemd) • Analyse the results (ptraj)

16. Information Flow in Amber PDB antechamber LEap Preparatory Programs Analysis Programs Topology and coordinate files mm-pbsa ptraj sander, pmemd, nmode Simulation Programs Simulation Results

17. Introduction to LEaP • The name LEaP is an acronym constructed from the names of the older AMBER software modules it replaces: link, edit, and parm. • Thus, LEaP can be used to prepare input for the AMBER molecular mechanics programs. • LEaP is the generic name given to the programs teLeap and xaLeap, which are generally run via the tleap and xleap shell scripts. • These two programs share a common command language • The xleap program has been enhanced through the addition of an X-windows graphical user interface.

18. Using tleap, the user can: • Read and write files in many formats (PDB, Mol2, Amber Prep, Amber Parm, Object File Format) • Construct new residues and molecules using simple commands • Link together residues and create nonbonded complexes of molecules • Place counterions around a molecule • Solvate molecules in arbitrary solvents • Modify internal coordinates within a molecule • Generate files that contain topology and parameters for AMBER.

19. With Xleap the user can: • Access commands using a simple point and click interface • Draw new residues and molecules in a graphical environment • View structures graphically • Graphically dock molecules • Modify the properties of atoms, residues, and molecules using a spreadsheet editor • Input or alter molecular mechanics parameters using a spreadsheet editor.

20. “Standard” Amber Amino Acid Residues • The N-terminal amino acid names and aliases are prefaced by the letter N (e.g. NALA for N-terminal ALA) and the C-terminal amino acids by the letter C (e.g.CALA) • Histidine can exist either as the protonated species or as a neutral species with a hydrogen at the delta or epsilon position. For this reason, the histidine name is either HIP, HID, or HIE (but not HIS). By default LEaP assigns the name HIS to HIE. • The AMBER force fields also differentiate between the residue cysteine (CYS) and the similar residue that participates in disulfide bridges, cystine (CYX).

21. Specifying a force field • There are now a variety of parameterizations, with no obvious "default" value. • The "traditional“ parameterization uses fixed partial charges, centered on atoms. Examples of this are ff94, ff99 and ff03 • The default in versions 8 and 9 of Amber would probably be ff03 or ff99SB, but users should consult the Amber manual

22. Specifying force field in LEaP xleap -s -f <filename>

23. Introduction to Antechamber • This is a set of tools to generate files for organic molecules, which can then be read into LEaP. • It can perform many file conversions, and can also assign atomic charges and atom types

24. Introduction to Sander • The acronym stands for Simulated Annealing with NMR-Derived Energy Restraints • Sander is the Amber module which carries out energy minimization, molecular dynamics, and NMR refinements.

25. Sander 9 Input Description sander [-help] [-O] [-A] -i mdin -o mdout -p prmtop -c inpcrd -r restrt -ref refc -x mdcrd -y inptraj -v mdvel -e mden -inf mdinfo -radii radii -cpin cpin -cpout cpout -cprestrt cprestrt -evbin evbin Output File Input File

26. Sander 9 Input Description for Simple Runs sander –O -i mdin -o mdout -p prmtop -c inpcrd Control data for the minimization/MD run Molecular topology, force field, periodic box type, atom and residue names Initial coordinates and (optionally) velocities and periodic box size

27. Preparation of control data for the minimization/MD run Each of the variables listed below is input in a namelist statement with the namelist identifier &cntrl. Keyword identifier End of namelist&cntrl Variables that are not given in the namelist input retain their default values.

28. Preparation of control data for Sander Toolbar Option description panel A Java program has been written to facilitate preparation of input job control files for Sander-8 (support for Sander-9 will be added soon). It uses intuitive controls to setup job control variables for Sander run. In many cases instead of variable's name it uses variable's description. For example, for variable NSTLIM it uses "Number of MD Steps (nstlim)". http://sf.anu.edu.au/~vvv900/cct/appl/sander8input/index.html

29. Preparation of control data for Sander Closely related options are grouped on separated panels which can be activated using tabs. Options can be setup using either text fields or combo boxes. http://sf.anu.edu.au/~vvv900/cct/appl/sander8input/index.html

30. Preparation of control data for Sander Advanced users might want to edit program options using the built-in text editor, with the program allowing easy switching between GUI and text editing http://sf.anu.edu.au/~vvv900/cct/appl/sander8input/index.html