Transcript Amber 8

Amber: How to set-up
calculations
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.
Preliminary Remarks
• Have a look at the Amber Home Page:
http://amber.scripps.edu
Preliminary Remarks:
Importance 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 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
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
Freeware Visualization Programs:
RasMol
http://www.openrasmol.org/
Freeware Visualization Programs:
VMD
http://www.ks.uiuc.edu/Research/vmd/
Freeware Visualization Programs:
gOpenMol
http://www.csc.fi/gopenmol/
http://sirius.sdsc.edu/
Freeware Visualization Programs:
Chimera
http://www.cgl.ucsf.edu/chimera/
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
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 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 Amber
PDB
antechamber
LEap
Preparatory Programs
Analysis Programs
Topology and
coordinate files
mm-pbsa
Simulation
Programs
ptraj
sander, pmemd,
nmode
Simulation Results
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.
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:
• 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
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 Cterminal 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 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 LEaP
xleap -s -f <filename>
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
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.
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
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
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.
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
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
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