Protein Local Optimization Program

 

PLOP is a program for protein modeling using all-atom energy functions.  It encapsulates all the algorithms I have developed (with collaborators), including multiscale Truncated Newton minimization, side chain optimization [1,2], loop prediction [3], and the prediction of helix positions and orientations [4].  It has been successfully used to refine homology models, relax protein-ligand complexes (i.e., induced fit effects), build models from experimental data [5], and investigate functionally relevant loop motions, due to post-translational modification and ligand binding [6,7]. 

 

PLOP was originally written by Matthew P. Jacobson, in collaboration with Richard A. Friesner, at Columbia University beginning in September 2000.  Since September 2002, the code has been maintained at UCSF, with contributions from both UCSF and Columbia.  The program has been licensed by both universities to Schrödinger, Inc. for commercial distribution as part of the PRIME (PRotein Integrated Modeling Environment) package. 

 

Recently, Prof. Victor Guallar and his group at Washington University, St. Louis, implemented their PELE method in the PLOP package.  Combining protein structure prediction algorithms and Metropolis Monte Carlo techniques, PELE provides a novel method to explore the long time dynamics energy landscapes of protein sized systems represented by all-atom force fields. The core of the technique is based on a steered localized perturbation followed by side chain sampling as well as minimization cycles.  Further details are available at http://spin.wustl.edu/pele/. 

 

The executable is available free of charge for academic purposes; licensing information is available here.

 

 

PLOP Manual

 

Acknowledgments

 

Info for PLOP Contributors

References

[1]  M. P. Jacobson, R. A. Friesner, Z. Xiang, and B. Honig. "On the Role of Crystal Packing Forces in Determining Protein Sidechain Conformations", Journal of Molecular Biology, 320 (2002) 597-608. PDF

 

[2]  M. P. Jacobson, G. A. Kaminski, R. A. Friesner, and C. S. Rapp. "Force Field Validation Using Protein Sidechain Prediction", Journal of Physical Chemistry B, 106 (2002) 11673-11680. PDF

 

[3]  M. P. Jacobson, D. L. Pincus, C. S. Rapp, T. J. F. Day, B. Honig, D. E. Shaw, and R. A. Friesner. "A Hierarchical Approach to All-Atom Loop Prediction", Proteins, 55 (2004) 351-367. PDF Supplementary Materials

 

[4]  X. Li, M. P. Jacobson, and R. A. Friesner. "High Resolution Prediction of Protein Helix Positions and Orientations", Proteins, 55 (2004) 368-382. PDF

 

[5]  M. Andrec, Y. Harano, M. P. Jacobson, R. A. Friesner, and R. M. Levy. "Complete Protein Structure Determination Using Backbone Residual Dipolar Couplings and Sidechain Rotamer Prediction", Journal of Structural and Functional Genomics, 2 (2002), pp. 103-111. PDF

 

[6]  V. Guallar, M. P. Jacobson, A. McDermott, and R. A. Friesner. "Computational Modeling of the Catalytic Reaction in Triose Phosphate Isomerase", Journal of Molecular Biology, 337 (2004) 227-239. PDF

 

[7]  C. Kalyanaraman, K. Bernacki, and M. P. Jacobson. "Virtual screening against highly charged active sites: Identifying substrates of alpha-beta barrel enzymes", Biochemistry, 44 (2005), pp. 2059-2071. PDF