Benchmarking a computational design method for the incorporation of metal ion-binding sites at symmetric protein interfaces

Protein Science : a Publication of the Protein Society
William A Hansen, Sagar D Khare

Abstract

The design of novel metal-ion binding sites along symmetric axes in protein oligomers could provide new avenues for metalloenzyme design, construction of protein-based nanomaterials and novel ion transport systems. Here, we describe a computational design method, symmetric protein recursive ion-cofactor sampling (SyPRIS), for locating constellations of backbone positions within oligomeric protein structures that are capable of supporting desired symmetrically coordinated metal ion(s) chelated by sidechains (chelant model). Using SyPRIS on a curated benchmark set of protein structures with symmetric metal binding sites, we found high recovery of native metal coordinating rotamers: in 65 of the 67 (97.0%) cases, native rotamers featured in the best scoring model while in the remaining cases native rotamers were found within the top three scoring models. In a second test, chelant models were crossmatched against protein structures with identical cyclic symmetry. In addition to recovering all native placements, 10.4% (8939/86013) of the non-native placements, had acceptable geometric compatibility scores. Discrimination between native and non-native metal site placements was further enhanced upon constrained energy minimization usi...Continue Reading

References

Dec 11, 1990·Biochemistry·L Regan, N D Clarke
May 1, 1995·Nature Structural Biology·M KlembaL Regan
Mar 31, 1994·Nature·D E RobertsonP L Dutton
Feb 7, 1998·Proceedings of the National Academy of Sciences of the United States of America·S KarlinK D Karlin
Sep 8, 1998·Current Opinion in Structural Biology·J R Desjarlais, N D Clarke
Jan 23, 1999·Current Opinion in Chemical Biology·D J TantilloK N Houk
Sep 1, 1999·Chemistry & Biology·S F Marino, L Regan
Dec 11, 1999·Nucleic Acids Research·H M BermanP E Bourne
Aug 15, 2000·Annual Review of Biophysics and Biomolecular Structure·D S Goodsell, A J Olson
Jun 6, 2003·Journal of the American Chemical Society·Wei YangJenny J Yang
Nov 30, 2006·Protein Science : a Publication of the Protein Society·Alexandre ZanghelliniDavid Baker
Aug 14, 2009·Nature·Kevin J WaldronNigel J Robinson
Aug 14, 2009·Nature·Yi LuNicholas M Marshall
Mar 3, 2010·Accounts of Chemical Research·Eric N SalgadoF Akif Tezcan
Apr 28, 2010·Proceedings of the National Academy of Sciences of the United States of America·Ying-Wu LinYi Lu
Dec 29, 2010·Methods in Enzymology·Andrew Leaver-FayPhilip Bradley
May 24, 2011·PloS One·Florian RichterDavid Baker
Jul 7, 2011·PloS One·Frank DiMaioIngemar André
Sep 8, 2011·Protein Science : a Publication of the Protein Society·Arthur LaganowskyTodd O Yeates
Nov 9, 2011·Proceedings of the National Academy of Sciences of the United States of America·Firas KhatibFoldit Players
Jan 25, 2012·Nature Chemistry·Melissa L ZastrowVincent L Pecoraro
Aug 9, 2013·Journal of the American Chemical Society·Jeremy H MillsDavid Baker
Oct 5, 2013·Biochemistry·Anindya RoyGiovanna Ghirlanda
Apr 30, 2014·Annual Review of Biophysics·Woon Ju SongF Akif Tezcan
Dec 2, 2014·Journal of the American Chemical Society·Anindya RoyGiovanna Ghirlanda
Apr 21, 2016·Methods in Molecular Biology·William A HansenSagar D Khare
Jul 1, 2016·Protein Engineering, Design & Selection : PEDS·Sharon L GuffyBrian Kuhlman
Dec 13, 2016·Proceedings of the National Academy of Sciences of the United States of America·Jeremy H MillsDavid Baker

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