This API provides a Python interface to use the updated LE4PD fortran codes developed by Jeremy Copperman and Marina Guenza. The codes use a coase-grained Langevin formalism to obtain site-specific dynamics of proteins. This formalism takes the structural ensemble available to the protein as input, and generates the relaxation dynamics analytically.
The following "non-standard" Python libraries MUST be installed for this code to work correctly:
The installation can be done simply with pip...
pip install -e .
One can also use the 'install.sh' file, which will also complile the FORTRAN files in the LE4PD/util directory.
To run the analysis, all that is required is a trajectory file in .g96 format and a .pdb file with the structure of the protein of interest. The .g96 file should have been processed to remove rigid body rotation and translational motions. These codes are set up to analyze MD trajectories of proteins generated using GROMACS (http://www.gromacs.org/). If you have a trajectory generated from another MD simulation engine, you can use a piece of software such as Open Babel (http://openbabel.org) to convert to .g96 format or 2) write your own code to convert to .g96 format. Future implementations might have to ability to accept other types of MD trajectory files
Examples for using LE4PD are located in LE4PD/examples. Two examples are present: ensemble and trajectory. LE4PD_ensemble_example shows how to set up the analysis for an ensemble of NMR experimental data from local files or fetched from the Protein Data Bank. LE4PD_trajectory_example performs the analysis on a 1ns simulation of Ubiquitin with modified residues.
Running the full LE4PD analysis (including saving the model to file) takes about 1 minute per 50 000 frames of trajectory data and scales approximately linearly up to 1 500 000 frames of trajectory data. These benchmarking data were generated running the code on the Comet supercomputer at the San Diego Supercomputing Center (https://www.sdsc.edu/support/user_guides/comet.html).
This implementation of the LE4PD code is still a work in progress. Right now, the code is only set up to perform an analysis of a trajectory of either a single protein or a complex of proteins. That is, we have not yet added the ability to analyze an ensemble of structures from a PDB file (as is described in the fourth reference in the list below). Coming soon!
It is possible that the f2py settings in the install.sh file will have to be tweaked based on individual machine architectures and installations.
- E. R. Beyerle and M. G. Guenza "Kinetics analysis of ubiquitin local fluctuations with Markov state modeling ofthe LE4PD normal modes"" Journal of Chemical Physics, 151, 164119 (2019) DOI:10.1063/1.5123513 .
- M. Dinpajooh, J. Copperman, E. R. Beyerle, and M. G. Guenza "Universality and Specificity in Protein Fluctuation Dynamics"" Physical Review Letters, 119, 158101 (2017) DOI:10.1103/PhysRevLett.119.158101 .
- J. Copperman and M. G. Guenza "Mode Localization in the Cooperative Dynamics of Protein Recognition"" Journal of Chemical Physics, 145, 015101 (2016) DOI:10.1063/1.4954506 .
- J. Copperman and M. G. Guenza "Predicting protein dynamics from structural ensembles” Journal of Chemical Physics, Invited Contribution for Special Topics Issue on Coarse Graining of Macromolecules, Biopolymers, and Membranes"" 143, 243131-12 (2015) doi: 10.1063/1.4935575.
- J. Copperman, M. G. Guenza "A Coarse-Grained Langevin Equation for Protein Dynamics: Global anisotropy and a mode approach to local complexity"" J. Phys. Chem. B, Festschrift issue honoring Branka Ladanyi, 119, 9195 (2015). DOI:10.1021/jp509473z.
- E. Caballero-Manrique, M. G. Guenza "A Langevin Equation Approach to Bridge Different Timescales of Relaxation in Protein Dynamics"" 51st Annual Meeting of the Biophysical Society, MAR 03-07, 2007. Biophysical Journal 377A (2007).