Master official page at Universitat Pompeu Fabra

High performance computing 2012

Synopsis

The focus of this course is to provide the tools, knowledge and practice to perform biochemical experiments on proteins and other molecules (drugs) in-silico using molecular dynamics simulations on a high performance computing infrastructure.

Target students
- Students with an interest in computing and simulation, structural biology, computational biophysics and biochemistry.
Requirements
- Courses: Attendance to the course MSI is recommended for this course.
- Programming: Use of medium to high level scripting is used in order to perform analysis on large simulation data sets.
- Knowledge: Interdisciplinary. Pharmaceutics, biochemistry, chemistry and biology will be an advantage to understand the molecular systems, computer science, physics and mathematics for the understanding of the fundamentals of the methodology.
Practical information
- Course length is 30 hours of classes (corresponding to 100 hours of personal work including classes) of which 4 hours are for the final project revision and defence.
- Room: all lectures will be in Aula 60.122, except the seminar
- Google calendar for the course
Evaluation
- 50% of final evaluation is based on exercises during the course
- 50% of final evaluation is based on research projects carried out by groups and defended publicly.
Picture and video gallery
- You Tube channel: http://www.youtube.com/user/ps3grid
- Flickr channel: http://www.flickr.com/photos/multiscalelab/with/3542248429/
- Vimeo channel: http://vimeo.com/user862246
Useful books:
- Computer Simulation of Liquids, Allen and Tildesley.
- Understanding Molecular Simulation, Second Edition: From Algorithms to Applications, Frenkel and Smit.
Lecturers: toni.giorgino-at-upf.edu and gianni.defabritiis-at-upf.edu

Resources and software

See the wiki page http://www.multiscalelab.org/master/HPC/resources .
Room: all lectures will be in Aula 60.122, except the seminar
Google calendar for the course

Course material

Class 1: Molecular dynamics hands-on
- Concept of classical dynamics
- The water molecule
- Amber and Charmm forcefields (bond, angle, dihedral, improper, Lennard-Jones, Coulomb)
- Protein data bank file 1NEY at RCSB
- CHARMM protein structure file: ionized.psf
- CHARMM parameter files par_all27_prot_lipid.prm
- Molecular dynamics codes
Class 2: Introduction to VMD
- http://www.ks.uiuc.edu/Training/Tutorials/vmd/tutorial-html/ (tutorial files http://www.ks.uiuc.edu/Training/Tutorials/vmd/)
- Use of the user guide http://www.ks.uiuc.edu/Research/vmd/current/ug.pdf
- Topics: Load molecule and navigate it, representations, selections (resname, name, type, resid), within of, same residue as, loading trajectories, keys (r,t,s,1,2)
- Example of Tcl scripting (atomselect, measure)
- Practice: VMD_exercise.txt, http://www.rcsb.org/pdb/explore.do?structureId=1ney
  - Example simulation result: PDB: ionized.pdb, PSF: ionized.psf, DCD: output_every_1ns.dcd
  - Filtered trajectory (loads into "protein" selection only): filtered.dcd
Class 3: Scripting in VMD (See slides for class 2)
- Advanced problem solutions using VMD scripting
Class 4: Practical (See slides for class 2)
- Counting TYR at the 1NEY dimer interface [chain B and resname TYR and (same residue as within 8 of (chain A and protein))]
- Diffusion coefficient of water in the example simulation
Class 5: Preparing a molecular structure for MD simulations
- Charmm topology files top_all27_prot_lipid.rtf
- Built from PDB in the Charmm format http://www.multiscalelab.org/acemd/protocols/ACETK.BLDCHARMM
- Relaxation and production run http://www.multiscalelab.org/acemd/protocols/ACETK.EQ
- Practice
Class 6: Building an AMBER system and molecule parametrization
- Build from PDB in the Amber format http://www.multiscalelab.org/acemd/protocols/ACETK.BLDAMBER
- Molecule parametrization using the Amber force field http://www.multiscalelab.org/acemd/protocols/ACETK.PRMAMBER
- Practice
Class 7: Advanced system building
- Embed a protein into a lipid bilayer (download mem.tgz)
- Practice
- Molecule parametrization using the Charmm force field http://www.multiscalelab.org/acemd/protocols/ACETK.PRMCHARMM
Class 8: Practical
Class 9: Biased free energy calculations: Metadynamics
- Theory behind metadynamics
- Practice
Class 10: Protein-ligand binding affinity calculations by umbrella sampling (See slides for previous class)
- Seminar
- Practice
Class 11: Seminar from PRBB Structural biology series: H. Grubmuller
- http://structure.prbb.org
- 9th march 2012 at 11AM at PRBB sala 173.06
Class 12: Langevin, free energies
- Theory behind Markov state models analysis
- Practice using simple Brownian dynamics
Class 13: Reconstructing the binding process by Markov state models (see previous slides)
- Seminar
- Practice
Class 14: Project review Final project
Class 15: Project defense

Exercises

Manipulation and analysis in VMD: see questions in slides for classes 2-4. Question n. 8 is: Compute the minimum distance of any two Tyr at opposite sides of the dimer interface. (Try to solve it in TCL only. If it helps, you can approximate the distance value within 0.1 A)
Compute the MSD(tau) and fit diffusion coefficient of water in the sample simulation provided (PSF: ionized.psf, DCD: output_every_1ns.dcd)
Discuss, prepare and run the structures indicated in the AMBER system building class.

Reading list

In addition to the protocols, read:

FAQ

sleap returns this Error: molecule and ion are both positive (or negative), can not make neutral
- The behavior of sleap and tleap differs with respect to addions. When you ask the addition of zero positive (negative) ions to an already positively (negatively) charged molecule, tleap will ignore the command, while sleap will error out. Just remove the offending line.

Projects

Analyze, discuss and prepare the following structures from the endocannabinoid system:

3HJU
3OLT
2ZKM
2PFR
... ?