1. AMBER

2. 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/

3. Basic Information Flow In Amber PDB File Preparatory Programs LEaP antechamber Simulation Programs Sander Gibbs NMode Analysis Programs Anal Ptraj Carnal Nmanal MM-PSA

4. Basic Information Flow In Amber PDB File Preparatory Programs LEaP antechamber Simulation Programs Sander Gibbs NMode Analysis Programs Anal Ptraj Carnal Nmanal MM-PSA

5. 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…

6. Preparatory Programs - Leap

7. Basic Information Flow In Amber PDB File Preparatory Programs LEaP antechamber Simulation Programs Sander Gibbs NMode Analysis Programs Anal Ptraj Carnal Nmanal MM-PSA

8. 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.

9. Sander Minimize Structure &cntrl imin=1, maxcyc=1000, ntb=0, ntpr=10, &end Restrain residues 1-100 1.0 RES 1 100 END Eof

10. Simulation Programs Gibbs –Concerned with free energy calculations. –Calculates the free energy difference,  G, between two states “0” and “1”

11. 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.

12. Basic Information Flow In Amber PDB File Preparatory Programs LEaP antechamber Simulation Programs Sander Gibbs NMode Analysis Programs Anal Ptraj Carnal Nmanal MM-PSA

13. 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

14. Analysis Programs Ptraj

15. 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

16. Analysis Programs Carnal

17. Analysis Programs Carnal

18. 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.

19. 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.

20. Useful Links General –http://amber.scripps.edu/ Tutorials –http://amber.scripps.edu/tutorial/index.html The amber archive –http://structbio.vanderbilt.edu/search.phtml

21. An Example Loop Dynamics of the HIV-1 Integrase Core Domain Use 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.

22. An Example PDB file – 1qs4 PREPARE tleap add a water box and counter ions to complete the model system ANALYSIS Ptraj MOVIE VMD SIMULATION Sander Energy minimisation, molecular dynamics

23. VMD /applic/vmd-1.8.2/bin/vmd