Generates structures by performing molecular normal mode analysis of input structure using the open-source molecular dynamics package ProDy.
The ProDy module is accessible from the Simulate section of the main menu.
The purpose of the module is perform generate normal mode trajectories of an input protein structure.
The input structure must be a complete structure without missing residues. Atom and residue naming should be compatible with those defined in the CHARMM force field for subsequent usage with certain other SASSIE modules. See Notes on Starting Structures and Force Fields and PDB Scan for further details.
For a system with N atoms, the 3N - 6 vibrational normal modes can be calculated. The first 6 represent translational and rotational degrees of freedom and are not included.
The output file format for the trajectories along each normal mode (ProDy_sampleModes) is DCD since in most cases many structures are generated. One can use Extract Utilities to convert DCD files to multi-frame PDB files. The trajectories are merged starting with 1st (non-trivial) normal mode and ending on last normal mode. Individual trajectories along each mode also appear in output. The DCD file for the merged trajectories is in XPLOR format, and cannot, in general, be read by ProDy (as is) for any subsequent (advanced input) usage.
The program uses the anisotropic network model (ANM) in ProDy to calculate normal modes. Default selections for the node atoms are CA atom for proteins; C2 atom for nucleic acids; C2 atom for sugars; Fe atom for hemes; C1 atom for lipids; ions; and O atom for water. User is refered to ProDy_AtomFlags for a list of acceptable ProDy residue names that fall under the above mentioned categories. All residues in the input PDB file should be named according to the ProDy convention, or removed from the input PDB file. The program will convert nucleotide names to Prody acceptable format for the user. Other residues must be named manually, and, if necessary (see first note above), named to be compatible with the CHARMM force field. For example, the ProDy program will execute with a either STE or STEA lipid residue names, but only STEA is CHARMM compatible.
The output file format for the ensemble of randomly sampled conformations from the normal modes (ProDy_sampleModes) is provided in both DCD and PDB format.
NOT YET IMPLEMENTED: An Advanced Input option to enter a prody application command (ProDy_Applications). The command must begin with either prody or evol, followed by the desired subcommand (eg. prody pca; evol fetch), followed by necessary options.
NOTE YET IMPLEMENTED: Advanced Input options to reject structures based on Rg value, position of atoms in the Z-direction and via atomic constraints provided as a list in a text file as described in Constraints. These options are not mutually exclusive and can be used in the same run as needed.
It is likely necessary and advisable to apply Energy Minimization to structures within the DCD files representing trajectories along the modes, or the ensemble of ramdomly sampled modes, to remove instances of physically unrealistic bond stretches that appear following the ProDy ANM calculation. As many as 5000 to 10000 steps of minimization may be needed for this.
A typical workflow involves generating trajectories along the requested number of normal modes of the input structure using this module, then energy minimizing the ensemble using Energy Minimization, then calculating scattering from the trajectory(s) (or randomly sampled ensemble) using modules in Calculate, and finally, comparing results to experimental data using modules in Analyze.
This example generates a set of 5 normal modes using the ProDy ANM module for the lysozyme protein.
run name User defined name of folder that will contain the results.
reference pdb PDB file with naming information and coordinates of the structure.
number of normal modes Number of normal modes to calculate.
number of conformations from sampled normal modes Number of conformations to generate by random sampling of normal modes (ProDy_sampleModes).
number of frames to traverse for each mode Number of steps to traverse each mode in both directions (ProDy_sampleModes).
average sampled RMSD Average RMSD of randomly sampled conformations with respect to initial conformation (ProDy_sampleModes).
maximum RMSD for normal mode trajectory Maximum RMSD of conformations for trajectory from traversed mode with respect to initial conformation (ProDy_sampleModes).
Results are written to a new directory within the given "run name" as noted in the output.
Several files are generated and saved to the "run name" prody directory: the output DCD file containing merged trajectories for modes 1 to 5; separate DCD files for individual trajectories along each mode; a DCD and PDB file with an ensemble of randomly-sampled conformations from each of the normal modes; a file containing the Kirchhoff matrix; a file containing the hessian matrix; a file with ANM results in NMD format for subsequent visualization; two additional files with ANM results in NMD format with normal modes extended to back-bone and all atoms, respectively; two text files with eigenvalues and eigenvectors, respectively; a text file containing square fluctuations along each mode; a text file with cross-correlations; a text file with the covariance matrix constructed using the 5 modes; and a text file with the β-value (temperature factor) of the course-grain atom on each residue.
The first image below shows an animation of the first (lowest frequency) normal mode. The image was generated by uploadng the file with normal modes extended to all atoms using the VMD Normal Mode Wizard. A short step-by-step guide to creating this image can be found on the VMD visualization/animation of normal modes page. A more detailed tutorial on the use of VMD's Normal Mode Wizard can be found on the ProDy_NMWiz tutorial site.
The three residues highlighted in yellow emphasize stretching of bonds to lengths that are not physically realistic.
The image below shows the analogous animation after the original trajectory for the first mode is subjected to 1000 steps of Energy Minimization.
This is further demonstrated in the third image below, which shows a plot of the root mean square deviation (RMSD), relative to input structure, versus frame number (for residue 118-the middle residue of the highlighted three) for the trajectory along the first mode from ProDy, before and after Energy Minimization.
This, shows that energy minimization can remove the physically unrealistic bond stretches, restoring those structures that deviate far from the initial input structure.
Below is an example of the inputs needed to perform a 1000 step Energy Minimization of the trajectory for the first normal mode, traverse_0.dcd.
Upon completion, the output screen should look something like the one below.
The trajectories for traverse0.dcd and mintraverse_0.dcd can be directly compared in VMD to see the effect of the 1000 step minimization.
output files from Prody
traverse_0.dcd First normal mode
traverse_1.dcd Second normal mode
traverse_2.dcd Third normal mode
traverse_3.dcd Fourth normal mode
traverse_4.dcd Fifth normal mode
lysozyme_samp.pdb Randomly-sampled conformations from each of the normal modes
lysozyme_samp.dcd (pdb and dcd formats)
output files from Energy Minimization
Advanced options are not yet implemented. ProDy will not run if the Check Box for Advanced Input is checked.
The input variables are listed below.
enter manual ProDy command ProDy (Evol) application command, subcommand, -options. (ProDy_Applications)
low Rg cutoff Structures with Rg values less than this value are discarded.
high Rg cutoff Structures with Rg values greater than this value are discarded.
check box to use atomic constraints Check box to implement the ability to discard structures that do not satisfy the atomic / geometric constraints provided in the user defined constraint file.
ProDy: Protein Dynamics Inferred from Theory and Experiments A. Bakan, L.M. Meireles, I. Bahar, Bioinformatics 27, 1575-1577 (2011). BIBTeX, EndNote, Plain Text
Dynamics of proteins predicted by molecular dynamics simulations and analytical approaches: Application to a-amylase inhibitor P. Doruker, A. R. Atilgan, I. Bahar, Proteins 40, 512-524 (2000). BIBTeX, EndNote, Plain Text
Anisotropy of fluctuation dynamics of proteins with an elastic network model A. R. Atilgan, S. R. Durrell, R. L. Jernigan, M. C. Demirel, O. Keskin, I. Bahar I. Biophys. J. 80, 505-515 (2001) BIBTex, Endnote, Plain Text
SASSIE: A program to study intrinsically disordered biological molecules and macromolecular ensembles using experimental scattering restraints J. E. Curtis, S. Raghunandan, H. Nanda, S. Krueger, Comp. Phys. Comm. 183, 382-389 (2012). BIBTeX, EndNote, Plain Text
Go to top