Difference between revisions of "Test System Repository"
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Currently direct editing is disabled for clarity of presentation; please visit [http://www.alchemistry.org/wiki/index.php/Talk:Test_System_Repository the discussion page] to add comments: | Currently direct editing is disabled for clarity of presentation; please visit [http://www.alchemistry.org/wiki/index.php/Talk:Test_System_Repository the discussion page] to add comments: | ||
| − | One of the biggest problems in careful comparisons and validations of methods is the difficulty of trying to agree on a single number for the free energy. If one is not sure of the value of the free energy, fine comparisons of methods are very difficult. Additionally, different programs with different bookkeeping, or parameters that have been rounded in some way can have legitimate small differences in the free energies, obscuring differences in the methods. | + | One of the biggest problems in careful comparisons and validations of methods is the difficulty of trying to agree on a single number for the free energy. If one is not sure of the value of the free energy, fine comparisons of methods are very difficult. Additionally, different programs with different bookkeeping, or parameters that have been rounded in some way can have legitimate small differences in the free energies, obscuring differences in the methods. Ideally test systems should have zero free energy. |
With a zero transformation, then it is necessary to partially specify the path, so that particularly clever methods do not manage to solve the problem in ways that would not be valid in general simulations. Because of this, the zero transformations here are defined with the endpoints and one midpoint along the transformation. This ensures that a large transformation is performed, but allows these systems to be used to improve free energy pathways as well. | With a zero transformation, then it is necessary to partially specify the path, so that particularly clever methods do not manage to solve the problem in ways that would not be valid in general simulations. Because of this, the zero transformations here are defined with the endpoints and one midpoint along the transformation. This ensures that a large transformation is performed, but allows these systems to be used to improve free energy pathways as well. | ||
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* Notes: There are no bond, angle or torsions terms, or solute/solvent charge: this is the simplest system that can be truly defined as realistic. | * Notes: There are no bond, angle or torsions terms, or solute/solvent charge: this is the simplest system that can be truly defined as realistic. | ||
| − | Problem 2) Can the free energy method handle multiple atomic sites efficiently? | + | Problem 2) Can the method handle water rearrangement around charges? |
| + | |||
| + | * System: Charged dipole on two LJ spheres tethered together. Currently testing +2/-2 charges, with 5 angstrom separation. The intermediate state is neutral. | ||
| + | |||
| + | Problem 3) Can the free energy method handle multiple atomic sites efficiently? | ||
* System: Napthalene null transform with benzene as intermediate, in TIP3P water | * System: Napthalene null transform with benzene as intermediate, in TIP3P water | ||
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* Notes: No ligand degrees of freedom to complicate the analysis. We are deciding whether this could also perform the anthracine->benzene->anthracine transformation. | * Notes: No ligand degrees of freedom to complicate the analysis. We are deciding whether this could also perform the anthracine->benzene->anthracine transformation. | ||
| − | + | * Notes: This setup allows avoidance of computing free energies of ions directly, which is still not handled completely correctly in many codes. | |
| − | |||
| − | * | ||
| − | + | Future problems to tackle: | |
| − | Problem 4) Can the method handle torsional degrees of freedom? | + | Problem 4) Can the method handle long time scale barriers along torsional degrees of freedom? |
| − | * | + | * Potential future system: 1-octanol -> ethane -> 1-octanol in TIP3P water. |
* Notes: Topologically, the system would be set up as HO-(CH2)14-OH, with the middle two carbons remaining coupled to the environment for the entire transformation. The h-bonds between alcohols and water might hopefully slow down the torsional sampling). | * Notes: Topologically, the system would be set up as HO-(CH2)14-OH, with the middle two carbons remaining coupled to the environment for the entire transformation. The h-bonds between alcohols and water might hopefully slow down the torsional sampling). | ||
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Problem 5) Can the method handle complications caused by putting all together in complex systems? | Problem 5) Can the method handle complications caused by putting all together in complex systems? | ||
| − | * System: Complicated substituted aromatic like Imatinib, with three substituted positions, with the transformation to cycle the substituents to different positions along the aromatic with benzene as the intermediate. | + | * Potential Future System: Complicated substituted aromatic like Imatinib, with three substituted positions, with the transformation to cycle the substituents to different positions along the aromatic with benzene as the intermediate. |
| − | + | Estimators of the uncertainty should be validated against uncertainty generated directly from runs from independent configurations (100), and should include the computation of the correlation time of the observable used to calculate the uncorrelated samples used in the free energies (such as the potential energy differences or dH/dL). | |
| − | + | 1. Input topology and parameter files in a number of different formats: | |
| + | |||
| + | * GROMACS | ||
| − | * | + | * AMBER |
| − | + | * DESMOND | |
| − | + | We are interested in getting validated comparisons with the following systems | |
* GROMOS | * GROMOS | ||
* CHARMM | * CHARMM | ||
| − | |||
| − | |||
| − | |||
| − | |||
* NAMD | * NAMD | ||
| − | |||
| − | |||
* DL_POLY | * DL_POLY | ||
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* LAMMPS | * LAMMPS | ||
| − | + | In each case, we have posted 100 starting configurations for each system, specifying initial box size and positions. We also list the exact energies of the starting configurations to make it easy to verify input files for additional programs. | |
| − | |||
| − | |||
4) Results from a number of different methods (TI, BAR, WHAM, Wang-Landau recursion). | 4) Results from a number of different methods (TI, BAR, WHAM, Wang-Landau recursion). | ||
Revision as of 09:47, 25 March 2011
Currently direct editing is disabled for clarity of presentation; please visit the discussion page to add comments:
One of the biggest problems in careful comparisons and validations of methods is the difficulty of trying to agree on a single number for the free energy. If one is not sure of the value of the free energy, fine comparisons of methods are very difficult. Additionally, different programs with different bookkeeping, or parameters that have been rounded in some way can have legitimate small differences in the free energies, obscuring differences in the methods. Ideally test systems should have zero free energy.
With a zero transformation, then it is necessary to partially specify the path, so that particularly clever methods do not manage to solve the problem in ways that would not be valid in general simulations. Because of this, the zero transformations here are defined with the endpoints and one midpoint along the transformation. This ensures that a large transformation is performed, but allows these systems to be used to improve free energy pathways as well.
Problem 1) Is the method at all valid for molecular systems?
- System: Simplest molecular free energy system = UA methane in TIP3P water.
- Notes: There are no bond, angle or torsions terms, or solute/solvent charge: this is the simplest system that can be truly defined as realistic.
Problem 2) Can the method handle water rearrangement around charges?
- System: Charged dipole on two LJ spheres tethered together. Currently testing +2/-2 charges, with 5 angstrom separation. The intermediate state is neutral.
Problem 3) Can the free energy method handle multiple atomic sites efficiently?
- System: Napthalene null transform with benzene as intermediate, in TIP3P water
- Notes: No ligand degrees of freedom to complicate the analysis. We are deciding whether this could also perform the anthracine->benzene->anthracine transformation.
- Notes: This setup allows avoidance of computing free energies of ions directly, which is still not handled completely correctly in many codes.
Future problems to tackle:
Problem 4) Can the method handle long time scale barriers along torsional degrees of freedom?
- Potential future system: 1-octanol -> ethane -> 1-octanol in TIP3P water.
- Notes: Topologically, the system would be set up as HO-(CH2)14-OH, with the middle two carbons remaining coupled to the environment for the entire transformation. The h-bonds between alcohols and water might hopefully slow down the torsional sampling).
Problem 5) Can the method handle complications caused by putting all together in complex systems?
- Potential Future System: Complicated substituted aromatic like Imatinib, with three substituted positions, with the transformation to cycle the substituents to different positions along the aromatic with benzene as the intermediate.
Estimators of the uncertainty should be validated against uncertainty generated directly from runs from independent configurations (100), and should include the computation of the correlation time of the observable used to calculate the uncorrelated samples used in the free energies (such as the potential energy differences or dH/dL).
1. Input topology and parameter files in a number of different formats:
- GROMACS
- AMBER
- DESMOND
We are interested in getting validated comparisons with the following systems
- GROMOS
- CHARMM
- NAMD
- DL_POLY
- TINKER
- LAMMPS
In each case, we have posted 100 starting configurations for each system, specifying initial box size and positions. We also list the exact energies of the starting configurations to make it easy to verify input files for additional programs.
4) Results from a number of different methods (TI, BAR, WHAM, Wang-Landau recursion).
- TI
- BAR, EXP, MBAR:
- Wang-Landau:
- Transition Matrix approaches
5) Optimization of variables
5a) Equilibrium methods
- For all: Spacing of states, pathway
- TI: numerical integration methods
- BAR: no others
- MBAR:no others
- DCMBAR: size of blocks, approximations in the dimension reduction of control variates.
5b) Equilibrium-at-limit methods
- For all : Spacing of states, pathway, MC or Gibbs sampling step type used
- Wang-Landau: The degree of flatness for decrementing the weight step, the magnitude of the weight step
- Transition state approaches: The transition kernel used