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Computational Design of Ligand Binding Proteins pp 47–62Cite as

Rosetta and the Design of Ligand Binding Sites

Part of the Methods in Molecular Biology book series (MIMB,volume 1414)

Abstract

Proteins that bind small molecules (ligands) can be used as biosensors, signal modulators, and sequestering agents. When naturally occurring proteins for a particular target ligand are not available, artificial proteins can be computationally designed. We present a protocol based on RosettaLigand to redesign an existing protein pocket to bind a target ligand. Starting with a protein structure and the structure of the ligand, Rosetta can optimize both the placement of the ligand in the pocket and the identity and conformation of the surrounding sidechains, yielding proteins that bind the target compound.

Key words

  • Computational design
  • Protein/small molecule interaction
  • Sequence optimization
  • Protein design
  • Ligand docking

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Acknowledgements

This work was supported through NIH (R01 GM099842, R01 DK097376, R01 GM073151) and NSF (CHE 1305874). RM is further partially supported by grant from the RosettaCommons.

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Authors and Affiliations

  1. Department of Chemistry, Vanderbilt University, Nashville, TN, 37235, USA

    Rocco Moretti, Brian J. Bender, Brittany Allison & Jens Meiler

  2. Center for Structural Biology, Vanderbilt University, Nashville, TN, 37235, USA

    Rocco Moretti, Brittany Allison & Jens Meiler

  3. Department of Pharmacology, Vanderbilt University, Nashville, TN, 37235, USA

    Brian J. Bender & Jens Meiler

Authors
  1. Rocco Moretti
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  2. Brian J. Bender
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Corresponding author

Correspondence to Jens Meiler .

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Editors and Affiliations

  1. Division of Basic Sciences, Fred Hutchinson Cancer Research Cen, Seattle, Washington, USA

    Barry L. Stoddard

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Moretti, R., Bender, B.J., Allison, B., Meiler, J. (2016). Rosetta and the Design of Ligand Binding Sites. In: Stoddard, B. (eds) Computational Design of Ligand Binding Proteins. Methods in Molecular Biology, vol 1414. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-3569-7_4

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  • DOI: https://doi.org/10.1007/978-1-4939-3569-7_4

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