amber: how to set-up calculations. preliminary remarks amber is a very sophisticated piece of...

Amber: How to set-up Amber: How to set-up calculationscalculations

Preliminary RemarksPreliminary 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.

Preliminary RemarksPreliminary Remarks

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

Preliminary Remarks:Preliminary Remarks:Importance of VisualizationImportance of Visualization

• One quick look at the structure can help to detect errors and save days or weeks of your time

Importance of Visualization: Real Life ExampleImportance of Visualization: Real Life ExampleA person spent many days trying to minimize a structure using Gaussian…

It was no success…

One quick look immediately discovered a problem

Problem

Importance of Visualization: Real Life ExampleImportance of Visualization: Real Life ExampleA 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.

Incomplete valencies on atoms…

Hydrogen atom is missing

Oxygen atom is missing

The structure also had a steric clash between two amino acid residues which could lead to a program overflow error

Freeware Visualization Programs:Freeware Visualization Programs:RasMolRasMol

http://www.openrasmol.org/

Freeware Visualization Programs:Freeware Visualization Programs:VMDVMD

http://www.ks.uiuc.edu/Research/vmd/

Freeware Visualization Programs:Freeware Visualization Programs:gOpenMolgOpenMol

http://www.csc.fi/gopenmol/

http://sirius.sdsc.edu/

Freeware Visualization Programs:Freeware Visualization Programs:ChimeraChimera

http://www.cgl.ucsf.edu/chimera/

Freeware Visualization Programs:Freeware Visualization Programs:JMolEditorJMolEditor

http://sf.anu.edu.au/~vvv900/cct/appl/jmoleditor/index.html

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

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…

Amber Basic TutorialsAmber Basic Tutorials• Amber distribution CD comes with several basic

tutorials(under amber9/tutorial):DNA Basic introduction to LEaP, sander, and ptraj, to build,

solvate, run MD and analyze trajectories.

Plastocyanin/ion/water Basic tutorial for a protein, introducing nonstandard residues, NMR restraints, and more complex modeling tasks.

Loop dynamics in HIV integrase

Show how a study of protein dynamical behavior was carried out, illustrating some more complex setups and analyses.

NMR refinement of DNA Basic introduction to NMR refinement using

LEaP and sander.

GB simulation Carrying out a protein simulation using the generalized Born continuum solvent model.

Additional tutorial examples are available at http://amber.scripps.edu.

Basic Steps for Running Simulation

1. Obtain starting Coordinates (PDB, NMR, Database, Program generated)

2. Run LEaP to generate the parameter and topology file.

3. Run Simulation (sander or pmemd)

4. Analyse the results (ptraj)

Information Flow in AmberInformation Flow in Amber

PDBantechamber

LEap

Topology andcoordinate files

sander, pmemd, nmode

Simulation Results

ptrajmm-pbsa

Analysis Programs

SimulationPrograms

Preparatory Programs

Introduction to LEaPIntroduction 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.

Using tleap, the user can: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.

With Xleap the user can: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.

““Standard” Amber Standard” Amber Amino Acid ResiduesAmino 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).

Specifying a force fieldSpecifying 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

Specifying force field in LEaPSpecifying force field in LEaP

xleap -s -f <filename>

Introduction to Introduction to AntechamberAntechamber

• 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

Introduction to SanderIntroduction 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.

Sander 9 Sander 9 Input DescriptionInput 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

Input FileOutput File

Sander 9 Sander 9 Input Description for Simple Input Description for Simple RunsRuns

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

Preparation of Preparation of control data for the control data for the minimization/MD runminimization/MD run

Each of the variables listed below is input in a namelist statement with the namelist identifier &cntrl.

End of namelist &cntrl

Keyword identifier

Variables that are not given in the namelist input retain their default values.

Preparation of Preparation of control data for Sandercontrol data for Sander

http://sf.anu.edu.au/~vvv900/cct/appl/sander8input/index.html

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)".

Option description

panel

Toolbar

Preparation of Preparation of control data for Sandercontrol data for Sander

http://sf.anu.edu.au/~vvv900/cct/appl/sander8input/index.html

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.

Preparation of Preparation of control data for Sandercontrol data for Sander

http://sf.anu.edu.au/~vvv900/cct/appl/sander8input/index.html

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