Open Access Highly Accessed Software

FreeContact: fast and free software for protein contact prediction from residue co-evolution

László Kaján1, Thomas A Hopf12, Matúš Kalaš34, Debora S Marks2 and Burkhard Rost156*

Author Affiliations

1 Department for Bioinformatics and Computational Biology, TU Munich, Boltzmannstraße 3, Garching 85748, Germany

2 Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, USA

3 Computational Biology Unit, Uni Computing, Bergen 5008, Norway

4 Department of Informatics, University of Bergen, Bergen 5008, Norway

5 Institute of Advanced Study (TUM-IAS), Lichtenbergstr. 2a, Garching/Munich 85748, Germany

6 WZW – Weihenstephan, Alte Akademie 8, Freising, Germany

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BMC Bioinformatics 2014, 15:85  doi:10.1186/1471-2105-15-85

Published: 26 March 2014



20 years of improved technology and growing sequences now renders residue-residue contact constraints in large protein families through correlated mutations accurate enough to drive de novo predictions of protein three-dimensional structure. The method EVfold broke new ground using mean-field Direct Coupling Analysis (EVfold-mfDCA); the method PSICOV applied a related concept by estimating a sparse inverse covariance matrix. Both methods (EVfold-mfDCA and PSICOV) are publicly available, but both require too much CPU time for interactive applications. On top, EVfold-mfDCA depends on proprietary software.


Here, we present FreeContact, a fast, open source implementation of EVfold-mfDCA and PSICOV. On a test set of 140 proteins, FreeContact was almost eight times faster than PSICOV without decreasing prediction performance. The EVfold-mfDCA implementation of FreeContact was over 220 times faster than PSICOV with negligible performance decrease. EVfold-mfDCA was unavailable for testing due to its dependency on proprietary software. FreeContact is implemented as the free C++ library “libfreecontact”, complete with command line tool “freecontact”, as well as Perl and Python modules. All components are available as Debian packages. FreeContact supports the BioXSD format for interoperability.


FreeContact provides the opportunity to compute reliable contact predictions in any environment (desktop or cloud).

Protein structure prediction; Protein sequence analysis; Fast protein contact prediction; 2D prediction; Open-source software; EVfold; EVcouplings; PSICOV; mfDCA; BioXSD; Debian package