GapRepairer: a server to model a structural gap and validate it using topological analysis

Motivation Over 25% of protein structures possess unresolved fragments. On the other hand, approximately 6% of protein chains have non-trivial topology (and form knots, slipknots, lassos and links). As the topology is fundamental for the proper function of proteins, modeling of topologically correct structures is decisive in various fields, including biophysics, biotechnology and molecular biology. However, none of the currently existing tools take into account the topology of the model and those which could be modified to include topology, demand experience in bioinformatics, protein topology and knot theory. Results In this work, we present the GapRepairer-the server that fills the gap in the spectrum of structure modeling methods. Its easy and intuitive interface offers the power of Modeller homology modeling to many non-experts in the field. This server determines the topology of templates and predicted structures. Such information when possible is used by the server to suggest the best model, or it can be used by the user to score models or to design artificially (dis)entangled structures. Availability and implementation GapRepairer server along with tutorials, usage notes, movies and the database of already repaired structures is available at http://gaprepairer.cent.uw.edu.pl. Supplementary information Supplementary data are available at Bioinformatics online.

[1]  Eugene I Shakhnovich,et al.  Identification of the minimal protein-folding nucleus through loop-entropy perturbations. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[2]  Matthew T. Weirauch,et al.  Rapid knot detection and application to protein structure prediction , 2006, ISMB.

[3]  Manuel C. Peitsch,et al.  SWISS-MODEL: an automated protein homology-modeling server , 2003, Nucleic Acids Res..

[4]  Marek Cieplak,et al.  Stabilizing effect of knots on proteins , 2008, Proceedings of the National Academy of Sciences.

[5]  A. Sali,et al.  Modeling of loops in protein structures , 2000, Protein science : a publication of the Protein Society.

[6]  Eric J. Rawdon,et al.  Conservation of complex knotting and slipknotting patterns in proteins , 2012, Proceedings of the National Academy of Sciences.

[7]  Ben M. Webb,et al.  Comparative Protein Structure Modeling Using MODELLER , 2007, Current protocols in protein science.

[8]  Shigeyuki Yokoyama,et al.  Methyl transfer by substrate signaling from a knotted protein fold , 2016, Nature Structural &Molecular Biology.

[9]  Joanna I. Sulkowska,et al.  Pierced Lasso Bundles Are a New Class of Knot-like Motifs , 2014, PLoS Comput. Biol..

[10]  Lukasz Goldschmidt,et al.  Structure and folding of a designed knotted protein , 2010, Proceedings of the National Academy of Sciences.

[11]  Jun Zhai,et al.  ArchPRED: a template based loop structure prediction server , 2006, Nucleic Acids Res..

[12]  Yang Zhang,et al.  I-TASSER server for protein 3D structure prediction , 2008, BMC Bioinformatics.

[13]  David Baker,et al.  Protein Structure Prediction Using Rosetta , 2004, Numerical Computer Methods, Part D.

[14]  Peng Wang,et al.  Single-molecule detection reveals knot sliding in TrmD denaturation. , 2013, Chemistry.

[15]  Pawel Dabrowski-Tumanski,et al.  PyLasso: a PyMOL plugin to identify lassos , 2017, Bioinform..

[16]  Neil P King,et al.  Knotted and topologically complex proteins as models for studying folding and stability. , 2007, Current opinion in chemical biology.

[17]  Pawel Dabrowski-Tumanski,et al.  In Search of Functional Advantages of Knots in Proteins , 2016, PloS one.

[18]  David Baker,et al.  Low free energy cost of very long loop insertions in proteins , 2003, Protein science : a publication of the Protein Society.

[19]  Pawel Dabrowski-Tumanski,et al.  Complex lasso: new entangled motifs in proteins , 2016, Scientific Reports.

[20]  Roy Wollman,et al.  Pierced Lasso Topology Controls Function in Leptin. , 2017, The journal of physical chemistry. B.

[21]  Johannes Söding,et al.  The HHpred interactive server for protein homology detection and structure prediction , 2005, Nucleic Acids Res..

[22]  Eric J. Rawdon,et al.  KnotProt: a database of proteins with knots and slipknots , 2014, Nucleic Acids Res..

[23]  José N Onuchic,et al.  Knotting pathways in proteins. , 2013, Biochemical Society transactions.

[24]  A. Shukla,et al.  Methodological advances: the unsung heroes of the GPCR structural revolution , 2015, Nature Reviews Molecular Cell Biology.

[25]  Eric J. Rawdon,et al.  LinkProt: a database collecting information about biological links , 2016, Nucleic Acids Res..

[26]  Pawel Dabrowski-Tumanski,et al.  Topological knots and links in proteins , 2017, Proceedings of the National Academy of Sciences.

[27]  Ben M. Webb,et al.  Comparative Protein Structure Modeling Using MODELLER , 2016, Current protocols in bioinformatics.

[28]  Neil P King,et al.  Identification of rare slipknots in proteins and their implications for stability and folding. , 2007, Journal of molecular biology.

[29]  Pawel Dabrowski-Tumanski,et al.  LassoProt: server to analyze biopolymers with lassos , 2016, Nucleic Acids Res..

[30]  Haruki Nakamura,et al.  Announcing the worldwide Protein Data Bank , 2003, Nature Structural Biology.

[31]  Kevin Karplus,et al.  Pokefind: a novel topological filter for use with protein structure prediction , 2009, Bioinform..

[32]  Pawel Dabrowski-Tumanski,et al.  To Tie or Not to Tie? That Is the Question , 2017, Polymers.