Solving protein structures using short-distance cross-linking constraints as a guide for discrete molecular dynamics simulations

Nicholas I. Brodie, Konstantin I. Popov, Evgeniy V. Petrotchenko, Nikolay V. Dokholyan, Christoph H. Borchers

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

We present an integrated experimental and computational approach for de novo protein structure determination in which short-distance cross-linking data are incorporated into rapid discrete molecular dynamics (DMD) simulations as constraints, reducing the conformational space and achieving the correct protein folding on practical time scales. We tested our approach on myoglobin and FK506 binding protein-models for α helix-rich and β sheet-rich proteins, respectively- and found that the lowest-energy structures obtained were in agreement with the crystal structure, hydrogen-deuterium exchange, surface modification, and long-distance cross-linking validation data. Our approach is readily applicable to other proteins with unknown structures.

Original languageEnglish (US)
Article numbere1700479
JournalScience Advances
Volume3
Issue number7
DOIs
StatePublished - Jul 5 2017

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Molecular Dynamics Simulation
Tacrolimus Binding Proteins
Proteins
Myoglobin
Deuterium
Protein Folding
Hydrogen

All Science Journal Classification (ASJC) codes

  • General

Cite this

Brodie, Nicholas I. ; Popov, Konstantin I. ; Petrotchenko, Evgeniy V. ; Dokholyan, Nikolay V. ; Borchers, Christoph H. / Solving protein structures using short-distance cross-linking constraints as a guide for discrete molecular dynamics simulations. In: Science Advances. 2017 ; Vol. 3, No. 7.
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Solving protein structures using short-distance cross-linking constraints as a guide for discrete molecular dynamics simulations. / Brodie, Nicholas I.; Popov, Konstantin I.; Petrotchenko, Evgeniy V.; Dokholyan, Nikolay V.; Borchers, Christoph H.

In: Science Advances, Vol. 3, No. 7, e1700479, 05.07.2017.

Research output: Contribution to journalArticle

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