AMBER

AMBER 7

• What is AMBER?– A collective name for a suite of programs

that allow users to carry out molecular dynamic simulations.

– And a set of molecular mechanical force fields for the simulation of biomolecules

– Has a number of useful programs…• Where is it?

– Available on /applic/amber7/

Basic Information Flow In Amber

PDB File Preparator

y Programs

LEaP

antechamber

Simulation

ProgramsSander

Gibbs

NMode

Analysis Program

sAnalPtraj

CarnalNmanalMM-PSA

Basic Information Flow In Amber

PDB File Preparator

y Programs

LEaP

antechamber

Simulation

ProgramsSander

Gibbs

NMode

Analysis Program

sAnalPtraj

CarnalNmanalMM-PSA

Preparatory Programs• Leap (used for proteins/nucleic acids)

– A generic name given to xleap and tleap– Xleap has a graphical user interface– Used to prepare the input for the AMBER

molecular mechanics program.

• What does it do?– Used to manipulate objects– Examples of objects; atoms, residues etc.– Can be used to set atom charge, identify the

position of disulphide bridges, delete bonds, addition of atoms, ions etc…

Preparatory Programs - Leap

Basic Information Flow In Amber

PDB File Preparator

y Programs

LEaP

antechamber

Simulation

ProgramsSander

Gibbs

NMode

Analysis Program

sAnalPtraj

CarnalNmanalMM-PSA

Simulation Programs

• Sander (Simulated Annealing with NMR-Derived Energy Restraints)

– Energy minimization, molecular dynamics and NMR refinements

– Provides direct support for several force fields for proteins and nucleic acids, and for several water models and other organic solvents.

Sander

Minimize Structure

&cntrl

imin=1, maxcyc=1000,

ntb=0,

ntpr=10,

&end

Restrain residues 1-100

1.0

RES 1 100

END

END

Eof

Simulation Programs

• Gibbs– Concerned with free energy

calculations.

– Calculates the free energy difference, G, between two states “0” and “1”

Simulation Programs

• Nmode– Performs molecular mechanics

calculations on proteins and nucleic acids.

– It uses first and second derivative information to find local minima, transition states, and to perform vibrational analysis.

Basic Information Flow In Amber

PDB File Preparator

y Programs

LEaP

antechamber

Simulation

ProgramsSander

Gibbs

NMode

Analysis Program

sAnalPtraj

CarnalNmanalMM-PSA

Analysis Programs• Ptraj

• A program to process/analyse 3-D coordinates/trajectories outputted from the AMBER programs.

• Includes•Calculate angles between atoms,•Compute and average structure over

all configurations read in.•Calculate pair distances in selected

atoms•Look at hydrogen bond

donors/acceptors

Analysis Programs• Ptraj

Analysis Programs• Anal

• Energy analysis module of AMBER, its key function is the decomposition of the energy among different groups of atoms in order to find the interaction energies between different parts of the structure

• Carnal• A coordinate analysis program• In addition to conventional trajectory

measurements it allows comparisons between multiple streams of coordinates

Analysis Programs• Carnal

Analysis Programs• Carnal

Other Programs•Protonate

–Add protons to a heavy-atom protein or DNA PDB file

•Ambpdb

–Produce the PDB file from the amber output.

•Pol_h

–Set positions of polar hydrogens in proteins.

•Gwh

–Set positions of polar hydrogens onto water oxygen positions.

Other Programs •MM-PBSA

•Post-proccessing method to evaluate free energies of binding of molecules in solution.

•Profec (Pictorial Representation Of Free Energy Changes)

•software tools for carrying out and displaying extraploative free energy calculations.

•Resp (Restrained ElectroStatic Potential)

•fits the quantum mechanically calculated electrostatic potential at molecular surfaces using an atom-centered point charge model.

Useful Links

• General– http://amber.scripps.edu/

• Tutorials– http://amber.scripps.edu/tutorial/index.html

• The amber archive– http://structbio.vanderbilt.edu/search.phtml

An Example Loop Dynamics of the HIV-1 Integrase

Core DomainUse AMBER to conduct molecular dynamics

simulations.There is a disordered surface loop near to the

active site and because surface loops are often involved in catalysis, understanding the conformational dynamics of the loop is important in understanding the catalytic mechanism.

An Example

PDB file – 1qs4

PREPARE

tleap add a water box and counter ions to complete the model system ANALYSIS

Ptraj

MOVIEVMD

SIMULATION

Sander

Energy minimisation, molecular dynamics

VMD

/applic/vmd-1.8.2/bin/vmd