A fast loop-closure algorithm to accelerate residue matching in computational enzyme design

Journal of Molecular Modeling
Jing XueYushan Zhu

Abstract

Constructing an active site on an inert scaffold is still a challenge in chemical biology. Herein, we describe the incorporation of a Newton-direction-based fast loop-closure algorithm for catalytic residue matching into our enzyme design program ProdaMatch. This was developed to determine the sites and geometries of the catalytic residues as well as the position of the transition state with high accuracy in order to satisfy the geometric constraints on the interactions between catalytic residues and the transition state. Loop-closure results for 64,827 initial loops derived from 21 loops in the test set showed that 99.51% of the initial loops closed to within 0.05 Å in fewer than 400 iteration steps, while the large majority of the initial loops closed within 100 iteration steps. The revised version of ProdaMatch containing the novel loop-closure algorithm identified all native matches for ten scaffolds in the native active-site recapitulation test. Its high speed and accuracy when matching catalytic residues with a scaffold make this version of ProdaMatch potentially useful for scaffold selection through the incorporation of more complex theoretical enzyme models which may yield higher initial activities in de novo enzyme des...Continue Reading

References

Jan 23, 1999·Current Opinion in Chemical Biology·D J TantilloK N Houk
Feb 24, 2001·Nature·C Walsh
Feb 24, 2001·Nature·A SchmidB Witholt
Nov 29, 2001·Proceedings of the National Academy of Sciences of the United States of America·D N Bolon, S L Mayo
Dec 19, 2001·Accounts of Chemical Research·R Wolfenden, M J Snider
Apr 30, 2003·Protein Science : a Publication of the Protein Society·Adrian A Canutescu, Roland L Dunbrack
Jan 22, 2004·Journal of Computational Chemistry·Evangelos A CoutsiasKen A Dill
Nov 1, 2006·Proceedings of the National Academy of Sciences of the United States of America·Jonathan Kyle LassilaStephen L Mayo
Nov 30, 2006·Protein Science : a Publication of the Protein Society·Alexandre ZanghelliniDavid Baker
Apr 24, 2007·Angewandte Chemie·Miguel D ToscanoDonald Hilvert
Mar 8, 2008·Science·Lin JiangDavid Baker
Mar 21, 2008·Nature·Daniela RöthlisbergerDavid Baker
May 2, 2009·Proteins·Christoph MalisiBirte Höcker
May 24, 2011·PloS One·Florian RichterDavid Baker
Jun 30, 2011·Protein Science : a Publication of the Protein Society·Yulin LeiYushan Zhu
Feb 24, 2012·Proceedings of the National Academy of Sciences of the United States of America·Heidi K PrivettStephen L Mayo
Apr 12, 2012·Protein Science : a Publication of the Protein Society·Geoffrey R Nosrati, K N Houk
May 12, 2012·Nature·U T BornscheuerK Robins
Aug 9, 2012·Journal of the American Chemical Society·Florian RichterDavid Baker
Mar 26, 2013·Angewandte Chemie·Gert KissK N Houk
May 8, 2013·Protein Science : a Publication of the Protein Society·Xiaoqiang HuangYushan Zhu
Jun 12, 2013·Annual Review of Biochemistry·Donald Hilvert
Nov 26, 2013·Trends in Biotechnology·George A KhouryChristodoulos A Floudas

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