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Torsion Angle Molecular Dynamics (Torsion Angle MD)

Performs torsion angle molecular dynamics of proteins, nucleic acids, carbohydrates and their complexes of input structures.

Accessibility

The Torsion Angle MD module is accessible from the Simulate section of the main menu.

Basic Usage

The purpose of the module is to perform molecular dynamics simulations of proteins, nucleic acids and/or carbohydrates by sampling backbone torsion angles using the TAMD module of CHARMM. The region of the molecule where the backbone torsion angles are sampled is referred to as the flexible region. Multiple flexible regions can be designated for a given segment of the molecule, and multiple segments in the molecule can contain flexible regions.

Notes

• CHARMM (version c38b1) is used as the simulation engine.

• Simulations can be performed with or without constraints for the radius of gyration of the molecule.

• TAMD automatically generates a CHARMM input script in which the harmonic constraint for the radius of gyration of the molecule is included.

• If a DCD file is selected as the input file then simulations are run on each frame.

Screen Shots and Description of Input Fields

Case 1: Protein without Rg constraint

Full length of HIV-1 Gag protein can be divided into five globular domains, specifically, the MA domain (residue 1-122), the N-terminal domain of CA (residues 144-276), the C-terminal of domain of CA (residues 282-353), the p2 spacer (residues 374-377), and the NC domain (residues 390-431). This example generates a series of structures to sample conformations of the the MA + N-terminal domain of CA (residues 1-276) using the Torsion Angle MD module. The flexible region consists of residues 123-143.

This example generates a trajectory from an input PDB without a Rg constraint.

• run name User defined name of folder that will contain the results.

• reference pdb PDB file with naming information and coordinates of the starting structure.

• input filename (dcd or pdb) File containing starting conformation(s) for simulation. The number of atoms must match that in the reference pdb. For files with multiple frames each one will be simulated.

• output file name (dcd) Filename for the output DCD contaiing the final frames resulting from simulation.

• number of preliminary minimization steps Number of steps of the conjugate gradient minimization to apply to each structure before Torsion Angle MD run.

• number of TAMD steps Number of steps of the Torsion Angle MD run.

• temperature (K) Simulation temperature.

• Rg force Force constant for TAMD with radius of gyration (RGYR) constraint.

• Rg value Target RGYR value in TAMD run with RGYR constraint (must be > 0 if Rg force > 0).

Complex Specific Input

• number of flexible segments An integer value indicating the number of regions to sample backbone torsions.

  • molecule type Select either protein or DNA or RNA.

  • flexible segment name Name of particular flexible segment.

  • number of flexible regions An integer value indicating the number of regions to sample backbone torsions.

  • flexible residue range(s) Residue numbers defining each flexible region in segment. The number of pairs should match the number of flexible regions for the given segment. Pairs of integers separated by hypens with each pair separated by commas.

Advanced Input Options

• check box to save individual trajectories Check box to save intermediate structures from each trajectory.

  • DCD write frequency Number of frames between saves to scratch DCD file. (Must be a factor of the number of TAMD steps.)

Example Output

./run_0/torsion_angle_md/gag_ma_nca.pdb    (original PDB file)
./run_0/torsion_angle_md/temp.inp          (TAMD input file)
./run_0/torsion_angle_md/min_00001.out     (TAMD output file)
./run_0/torsion_angle_md/tamd_noconstraint.dcd  (final TAMD trajectory)
./run_0/torsion_angle_md/tamd_dyn_00001.dcd     (all saved trajectories)
./run_0/torsion_angle_md/tamd_output.pdb   (PDB file created by TAMD)
./run_0/torsion_angle_md/tamd_output.psf   (PSF file created by TAMD)
./run_0/torsion_angle_md/tamd.tree         (TAMD tree file)
./run_0/torsion_angle_md/tamd.loops.rst    (TAMD restart file)
./run_0/torsion_angle_md/temp_0.pdb        (temporary PDB file)

Files Used and Created in Example

• input files

  gag_ma_nca.pdb

• output files

  A zipped file with all of the TAMD output files can be downloaded below.

  tamd_noconstraint_output.zip

Case 2: Protein with Rg constraint

This example applies a Rg constraint for the input structure while TAMD sampling.

Example Output

Files Used and Created in Example

• input files

  gag_ma_nca.pdb

• output files

  A zipped file with all of the TAMD output files can be downloaded below.

  tamd_rgconstraint_output.zip

Visualization

TAMD simulations of 100 ps were performed on the HIV-1 Gag protein MA + N-terminal CA domains with and without a Rg constraint. Applying the constraint prevent the collapse of the molecule that occurs due to the limitations of current implict solvent models used in the CHARMM force field. The figure below shows the time trajectories of Rg (RGYR) for three different intitial conformations of the starting molecule with (solid lines) and without (dashed lines) the Rg constraint.

Case 3: Single-stranded RNA no Rg constraint (short run)

A short (1000 step) TAMD simulation is performed on a 80-nucleotide portion of an intron from the HIV-1 viral single-stranded RNA to illustrate how to use the Torsion Angle MD module with RNA molecules. The flexible regions are residues 24-30 and residues 47-55.

This example generates a trajectory from an input PDB without a Rg constraint.

Complex Specific Input

• number of flexible segments An integer value indicating the number of regions to sample backbone torsions.

  • molecule type Select either protein or DNA or RNA.

  • flexible segment name Name of particular flexible segment.

  • number of flexible regions An integer value indicating the number of regions to sample backbone torsions.

  • flexible residue range(s) Residue numbers defining each flexible region in segment. The number of pairs should match the number of flexible regions for the given segment. Pairs of integers separated by hypens with each pair separated by commas.

Example Output

./run_1/torsion_angle_md/trunc2a_min.pdb    (original PDB file)
./run_1/torsion_angle_md/temp.inp          (TAMD input file)
./run_1/torsion_angle_md/min_00001.out     (TAMD output file)
./run_1/torsion_angle_md/tamd_noconstraint.dcd  (final TAMD trajectory)
./run_1/torsion_angle_md/tamd_dyn_00001.dcd     (all saved trajectories)
./run_1/torsion_angle_md/tamd_output.pdb   (PDB file created by TAMD)
./run_1/torsion_angle_md/tamd_output.psf   (PSF file created by TAMD)
./run_1/torsion_angle_md/tamd.tree         (TAMD tree file)
./run_1/torsion_angle_md/tamd.loops.rst    (TAMD restart file)
./run_1/torsion_angle_md/temp_0.pdb        (temporary PDB file)

Files Used and Created in Example

• input files

  trunc2a_min.pdb

• output files

  A zipped file with all of the TAMD output files can be downloaded below.

  tamd_rna_noconstraint_output.zip

Case 4: Linear B-form dsDNA no Rg constraint (short run)

A short (1000 step) TAMD simulation is performed on a 60 base pair B-form double stranded DNA molecule to illustrate how to use the Torsion Angle MD module with dsDNA molecules. The entire molecule, excluding the first and last residues in each strand will be assigned as the flexible regions.

NOTE: Residues are numbered continuously from 1 to 120 (1-60 for segment DNA1 and 61-120 for segment DNA2). Residue numbering is from the 5' to 3' direction of DNA1, continuing from the 5' to 3' direction of DNA2.

This example generates a trajectory from an input PDB without a Rg constraint.

Complex Specific Input

• number of flexible segments An integer value indicating the number of regions to sample backbone torsions.

  • molecule type Select either protein or DNA or RNA.

  • flexible segment name Name of particular flexible segment.

  • number of flexible regions An integer value indicating the number of regions to sample backbone torsions.

  • flexible residue range(s) Residue numbers defining each flexible region in segment. The number of pairs should match the number of flexible regions for the given segment. Pairs of integers separated by hypens with each pair separated by commas.

Example Output

./run_2/torsion_angle_md/c36_dsDNA60_min.pdb    (original PDB file)
./run_2/torsion_angle_md/temp.inp          (TAMD input file)
./run_2/torsion_angle_md/min_00001.out     (TAMD output file)
./run_2/torsion_angle_md/tamd_noconstraint.dcd  (final TAMD trajectory)
./run_2/torsion_angle_md/tamd_dyn_00001.dcd     (all saved trajectories)
./run_2/torsion_angle_md/tamd_output.pdb   (PDB file created by TAMD)
./run_2/torsion_angle_md/tamd_output.psf   (PSF file created by TAMD)
./run_2/torsion_angle_md/tamd.tree         (TAMD tree file)
./run_2/torsion_angle_md/tamd.loops.rst    (TAMD restart file)
./run_2/torsion_angle_md/temp_0.pdb        (temporary PDB file)

Files Used and Created in Example

• input files

  c36_dsDNA60_min.pdb

• output files

  A zipped file with all of the TAMD output files can be downloaded below.

  tamd_dna_noconstraint_output.zip

Reference(s) and Citations

1. Application of torsion angle molecular dynamics for efficient sampling of protein conformations J. Chen, W. Im, C. L. Brooks III, J. Comput. Chem. 26 1565-1578 (2005). BIBTeX, EndNote, Plain Text

2. A coupled implicit method for chemical non-equilibrium flows at all speeds S. Jian, K. H. Chen, Y. Choi, J. Comput. Phys. 106 306-318 (1993). BIBTeX, EndNote, Plain Text

3. CHARMM: The energy function and its parameterization with an overview of the program A. D. MacKerel Jr., C. L. Brooks III, L. Nilsson, B. Roux, Y. Won, M. Karplus, The Encyclopedia of Computational Chemistry, John Wiley & Sons: Chichester, 271-277 (1998). BIBTex, Endnote, Plain Text

4. Combined Monte Carlo Torsion-Angle Molecular Dynamics for Ensemble Modeling of Proteins, Nucleic Acids and Carbohydrates W. Zhang, S. C. Howell, D. W. Wright, A. Heindel, X. Qiu, J. Che, J. E. Curtis, J. Mol. Graph. Mod. 73 179-190 (2017). BIBTex, Endnote, Plain Text

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