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Software Developed by the Donald Lab

OSPREY

Other software:
OSPREY
DISCO
LibProtNMR
RDC-PANDA
NASCA
POOL
Q5
CRANS

Software previously released by the Donald Lab:
Exact-2NH
MTC
NVR/HD/GD
Rage/Enrage

Download | User Manual | License | Q&A | Contact | Other Versions | Bibliography

Welcome to the website for the OSPREY (Open Source Protein REdesign for You) software.

Quick start: A comprehensive description of the software's capabilities is available here. For support, please visit our new Q&A page.

Here, you can download the newest version of the software, read the latest user manual and license agreement, or e-mail inquiries. The latest version of OSPREY is v2.1 beta. The latest stable release is version v2.0 (downloadable here). The main difference between these versions is that the new DEEPer algorithm for backbone flexibility has been added to version 2.1 beta; most of the functionality in the two versions is identical.

OSPREY is a suite of programs for computational structure-based protein design. OSPREY is developed in the lab of Prof. Bruce Donald at Duke University. Citations to the primary papers for our work can be found here.

OSPREY is specifically designed to identify protein mutants that possess desired target properties (e.g., improved stability, switch of substrate specificity, etc.). OSPREY can also be used for predicting small-molecule drug inhibitors. Starting with version 2.0, OSPREY can now design protein-protein and protein-peptide interactions.

OSPREY incorporates several different algorithmic modules for structure-based protein design, including a number of powerful Dead-End Elimination algorithms and the ensemble-based K* algorithm for protein-ligand binding prediction. OSPREY allows the incorporation of continuous protein side-chain and continuous or discrete backbone flexibility, while maintaining provable guarantees with respect to the input model (input structure, rotamer library, energy function, and any backbone perturbations) for a given protein design problem. See full details of the different algorithmic modules in OSPREY.

To our knowledge, OSPREY is the only open-source, freely-available implementation of the DEE/A* algorithms. DEE/A* combines the provable Dead-End Elimination (DEE) algorithms with the A* search enumeration. OSPREY also includes many extensions and improvements to the DEE framework (e.g., minDEE, iMinDEE, K*, DACS, BD, BRDEE, DEEPer). These extensions improve efficiency and allow the modelling of molecular flexibility. OSPREY includes the K* (pronounced "K-star") module, which is a provably-good ε-approximation (epsilon-approximation) algorithm for computing binding constants (KD) over molecular ensembles of the bound and unbound states of a protein:ligand complex using minimized DEE/A* (namely, minDEE/A*/K*). See the OSPREY manual and our papers for details. A shorter list of the primary papers underlying our software can be found here.

The current stable release of OSPREY is 2.0. Version 2.0 includes several new features including: Version 2.1 beta includes these features in addition to an implementation of the DEEPer algorithm, featuring seven types of backbone perturbations for use in either K* or single-structure-based designs.

OSPREY has been ported to GPUs. This enables the user to utilize GPUs to accelerate the process of protein design in a massively-parallel fashion. This port was done by Michael Zeng who received a Ph.D. in 2011 from our lab (Michael is a professor at IIIS, Tshingua University now). You can read our ISMB/Bioinformatics paper, download the GPU version here from github, and we provide a gzipped TAR archive here on our site.

OSPREY is free software and can be redistributed and/or modified under the terms of the GNU Lesser General Public License as published by the Free Software Foundation, either version 3 of the License, or (optionally) any later version. OSPREY is distributed in the hope that it will be useful, but WITHOUT ANY WARRANTY; without even the implied warranty of MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the GNU Lesser General Public License for more details. Full licensing details, including citation requirements for the various different modules of the software, are found here.

Selected Empirical Designs that used OSPREY:

  1. R. Rudicell, Y. Kwon, S.Y. Ko, A. Pegu, M. Louder, I. Georgiev, X. Wu, J. Zhu, J. Boyington, X. Chen, W. Shi, Z. Yang, N. Doria-Rose, K. McKee, S. O'Dell, S. Schmidt, G.Y. Chuang, A. Druz, C. Soto, Y. Yang, B. Zhang, T. Zhou, J.P. Todd, K. Lloyd, J. Eudailey, K. Roberts, B. R. Donald, R. Bailer, J. Ledgerwood, NISC Comparative Sequencing Program, J. Mullikin, L. Shapiro, R. Koup, B. Graham, M. Nason, M. Connors, B. Haynes, S. Rao, M. Roederer, P. Kwong, J. Mascola, and G. Nabel. Enhanced potency of a broadly neutralizing HIV-1 antibody in vitro improves protection against lentiviral infection in vivo. Journal of Virology (2014) doi: 10.1128/JVI.02213-14
  2. Ivelin S. Georgiev, Rebecca S. Rudicell, Kevin O. Saunders, Wei Shi, Tatsiana Kirys, Krisha McKee, Sijy O'Dell, Gwo-Yu Chuang, Zhi-Yong Yang, Gilad Ofek, Mark Connors, John R. Mascola, Gary J. Nabel and Peter D. Kwong. Antibodies VRC01 and 10E8 Neutralize HIV-1 with High Breadth and Potency Even with Ig-Framework Regions Substantially Reverted to Germline. The Journal of Immunology (2014). doi: 10.4049/.jimmunol.1302515
  3. I. Georgiev, P. Acharya, S. Schmidt, Y. Li, D. Wycuff, G. Ofek, N. Doria-Rose, T. Luongo, Y, Yang, T. Zhou, B. R. Donald, J. Mascola, P. Kwong. Design of Epitope-Specific Probes for Sera Analysis and Antibody Isolation. Retrovirology 2012; 9(Suppl.2):P50.
  4. Roberts KE, Cushing PR, Boisguerin P, Madden DR, Donald BR. Computational Design of a PDZ Domain Peptide Inhibitor that Rescues CFTR Activity. PLoS Comput Biol. 2012 Apr;8(4):e1002477. Epub 2012 Apr 19. PubMed PMID: 22532795; PubMed Central PMCID: PMC3330111.
  5. Frey KM, Georgiev I, Donald BR, Anderson AC. Predicting resistance mutations using protein design algorithms. Proc Natl Acad Sci U S A. 2010 Aug 3;107(31):13707-12. Epub 2010 Jul 19. PubMed PMID: 20643959; PubMed Central PMCID: PMC2922245.
  6. Chen CY, Georgiev I, Anderson AC, Donald BR. Computational structure-based redesign of enzyme activity. Proc Natl Acad Sci U S A. 2009 Mar 10;106(10):3764-9. Epub 2009 Feb 19. PubMed PMID: 19228942; PubMed Central PMCID: PMC2645347.
  7. Gorczynski MJ, Grembecka J, Zhou Y, Kong Y, Roudaia L, Douvas MG, Newman M, Bielnicka I, Baber G, Corpora T, Shi J, Sridharan M, Lilien R, Donald BR, Speck NA, Brown ML, Bushweller JH. Allosteric inhibition of the protein-protein interaction between the leukemia-associated proteins Runx1 and CBFbeta. Chem Biol. 2007 Oct;14(10):1186-97. PubMed PMID: 17961830.
  8. Stevens BW, Lilien RH, Georgiev I, Donald BR, Anderson AC. Redesigning the PheA domain of Gramicidin Synthetase leads to a new understanding of the enzyme's mechanism and selectivity. Biochemistry. 2006 Dec 26;45(51):15495-504. Epub 2006 Dec 19. PubMed PMID: 17176071.
Selected Crystal Stuctures That Confirmed OSPREY Designs:
  1. Staphylococcus Aureus V31y, F92i Mutant Dihydrofolate Reductase Complexed With Nadph And 5-[(3s)-3-(5-Methoxy-2',6'-Dimethylbiphenyl- 3-Yl)but-1-Yn-1-Yl]-6-Methylpyrimidine-2,4-Diamine [Oxidoreductase... Taxonomy: Staphylococcus aureus Proteins: 2 Chemicals: 2 modified: 2011/05/27 MMDB ID: 83621 PDB ID: 3LG4
  2. Staphylococcus Aureus Dihydrofolate Reductase Complexed With Nadph And 2,4-Diamino-5-[3-(3-Methoxy-5-(2,6-Dimethylphenyl)phenyl)but-1-Ynyl]- 6-Methylpyrimidine [Oxidoreductase, EC: 1.5.1.3] Taxonomy: Staphylococcus aureus RF122 Proteins: 1 Chemicals: 2 modified: 2011/05/26 MMDB ID: 77139 PDB ID: 3F0Q

    Search PDB (NCBI) for all our protein structures (NMR, X-ray)

The Book, and Selected Papers on OSPREY Algorithms, Methodology, and Validation:
    The textbook describes the algorithms in detail: Algorithms in Structural Molecular Biology. MIT Press (2011).
    Order from Amazon.




  1. P. Gainza, K. Roberts, I. Georgiev, R. Lilien, D. Keedy, C.-Y. Chen, F. Reza, A Anderson, D. Richardson, J. Richardson, and B. R. Donald. OSPREY: Protein design with ensembles, flexibility, and provable algorithms. Methods in Enzymology, Vol. 523, Methods in Protein Design, pp87-107. (2013). ISBN: 9780123942920.
    http://store.elsevier.com/Methods-in-Protein-Design/isbn-9780123942920/
  2. Hallen MA, Keedy DA, Donald BR. Dead-End Elimination with Perturbations (DEEPer): A Provable Protein Design Algorithm with Continuous Sidechain and Backbone Flexibility. Proteins. 2012, in press. Epub 2012 Jul 21. PubMed PMID: 22821798.
  3. Y. Zhou, W. Xu, B. R. Donald, and J. (Michael) Zeng. An efficient parallel algorithm for accelerating computational protein design. Bioinformatics. 2014 Jun 15;30(12):i255-i263. Proceedings of ISMB, Boston, MA. doi: 10.1093/bioinformatics/btu264.
  4. Roberts KE, Cushing PR, Boisguerin P, Madden DR, Donald BR. Computational Design of a PDZ Domain Peptide Inhibitor that Rescues CFTR Activity. PLoS Comput Biol. 2012 Apr;8(4):e1002477. Epub 2012 Apr 19. PubMed PMID: 22532795; PubMed Central PMCID: PMC3330111.
  5. Gainza P, Roberts KE, Donald BR. Protein design using continuous rotamers. PLoS Comput Biol. 2012 Jan;8(1):e1002335. Epub 2012 Jan 12. PubMed PMID: 22279426; PubMed Central PMCID: PMC3257257.
  6. Frey KM, Georgiev I, Donald BR, Anderson AC. Predicting resistance mutations using protein design algorithms. Proc Natl Acad Sci U S A. 2010 Aug 3;107(31):13707-12. Epub 2010 Jul 19. PubMed PMID: 20643959; PubMed Central PMCID: PMC2922245.
  7. Chen CY, Georgiev I, Anderson AC, Donald BR. Computational structure-based redesign of enzyme activity. Proc Natl Acad Sci U S A. 2009 Mar 10;106(10):3764-9. Epub 2009 Feb 19. PubMed PMID: 19228942; PubMed Central PMCID: PMC2645347.
  8. Georgiev I, Keedy D, Richardson JS, Richardson DC, Donald BR. Algorithm for backrub motions in protein design. Bioinformatics. 2008 Jul 1;24(13):i196-204. PubMed PMID: 18586714; PubMed Central PMCID: PMC2718647.
  9. Georgiev I, Donald BR. Dead-end elimination with backbone flexibility. Bioinformatics. 2007 Jul 1;23(13):i185-94. PubMed PMID: 17646295.
  10. Georgiev I, Lilien RH, Donald BR. The minimized dead-end elimination criterion and its application to protein redesign in a hybrid scoring and search algorithm for computing partition functions over molecular ensembles. J Comput Chem. 2008 Jul 30;29(10):1527-42. PubMed PMID: 18293294; PubMed Central PMCID: PMC3263346.
  11. Lilien RH, Stevens BW, Anderson AC, Donald BR. A novel ensemble-based scoring and search algorithm for protein redesign and its application to modify the substrate specificity of the Gramicidin Synthetase A phenylalanine adenylation enzyme. J Comput Biol. 2005 Jul-Aug;12(6):740-61. PubMed PMID: 16108714.
  12. Georgiev I, Lilien RH, Donald BR. Improved Pruning algorithms and Divide-and-Conquer strategies for Dead-End Elimination, with application to protein design. Bioinformatics. 2006 Jul 15;22(14):e174-83. PubMed PMID: 16873469.