Combined and iterative use of computational design and directed evolution for protein-ligand binding design

Meng Wang, Huimin Zhao

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

The advantages of computational design and directed evolution are complementary, and only through combined and iterative use of both approaches, a daunting task such as protein-ligand interaction design, can be achieved efficiently. Here, we describe a systematic strategy to combine structure-guided computational design, iterative site saturation mutagenesis, and yeast two-hybrid system (Y2H)-based phenotypic screening to engineer novel and orthogonal interactions between synthetic ligands and human estrogen receptor α (hERα) for the development of novel gene switches.

Original languageEnglish (US)
Title of host publicationMethods in Molecular Biology
PublisherHumana Press Inc.
Pages139-153
Number of pages15
DOIs
StatePublished - May 1 2016

Publication series

NameMethods in Molecular Biology
Volume1414
ISSN (Print)1064-3745

Fingerprint

Protein Binding
Switch Genes
Ligands
Two-Hybrid System Techniques
Mutagenesis
Estrogen Receptors
Proteins

Keywords

  • Computational design
  • Directed evolution
  • Gene switch
  • Protein-ligand interaction

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

Cite this

Wang, M., & Zhao, H. (2016). Combined and iterative use of computational design and directed evolution for protein-ligand binding design. In Methods in Molecular Biology (pp. 139-153). (Methods in Molecular Biology; Vol. 1414). Humana Press Inc.. https://doi.org/10.1007/978-1-4939-3569-7_8

Combined and iterative use of computational design and directed evolution for protein-ligand binding design. / Wang, Meng; Zhao, Huimin.

Methods in Molecular Biology. Humana Press Inc., 2016. p. 139-153 (Methods in Molecular Biology; Vol. 1414).

Research output: Chapter in Book/Report/Conference proceedingChapter

Wang, M & Zhao, H 2016, Combined and iterative use of computational design and directed evolution for protein-ligand binding design. in Methods in Molecular Biology. Methods in Molecular Biology, vol. 1414, Humana Press Inc., pp. 139-153. https://doi.org/10.1007/978-1-4939-3569-7_8
Wang M, Zhao H. Combined and iterative use of computational design and directed evolution for protein-ligand binding design. In Methods in Molecular Biology. Humana Press Inc. 2016. p. 139-153. (Methods in Molecular Biology). https://doi.org/10.1007/978-1-4939-3569-7_8
Wang, Meng ; Zhao, Huimin. / Combined and iterative use of computational design and directed evolution for protein-ligand binding design. Methods in Molecular Biology. Humana Press Inc., 2016. pp. 139-153 (Methods in Molecular Biology).
@inbook{9d4995e65af6426e89165c57e91d7389,
title = "Combined and iterative use of computational design and directed evolution for protein-ligand binding design",
abstract = "The advantages of computational design and directed evolution are complementary, and only through combined and iterative use of both approaches, a daunting task such as protein-ligand interaction design, can be achieved efficiently. Here, we describe a systematic strategy to combine structure-guided computational design, iterative site saturation mutagenesis, and yeast two-hybrid system (Y2H)-based phenotypic screening to engineer novel and orthogonal interactions between synthetic ligands and human estrogen receptor α (hERα) for the development of novel gene switches.",
keywords = "Computational design, Directed evolution, Gene switch, Protein-ligand interaction",
author = "Meng Wang and Huimin Zhao",
year = "2016",
month = "5",
day = "1",
doi = "10.1007/978-1-4939-3569-7_8",
language = "English (US)",
series = "Methods in Molecular Biology",
publisher = "Humana Press Inc.",
pages = "139--153",
booktitle = "Methods in Molecular Biology",

}

TY - CHAP

T1 - Combined and iterative use of computational design and directed evolution for protein-ligand binding design

AU - Wang, Meng

AU - Zhao, Huimin

PY - 2016/5/1

Y1 - 2016/5/1

N2 - The advantages of computational design and directed evolution are complementary, and only through combined and iterative use of both approaches, a daunting task such as protein-ligand interaction design, can be achieved efficiently. Here, we describe a systematic strategy to combine structure-guided computational design, iterative site saturation mutagenesis, and yeast two-hybrid system (Y2H)-based phenotypic screening to engineer novel and orthogonal interactions between synthetic ligands and human estrogen receptor α (hERα) for the development of novel gene switches.

AB - The advantages of computational design and directed evolution are complementary, and only through combined and iterative use of both approaches, a daunting task such as protein-ligand interaction design, can be achieved efficiently. Here, we describe a systematic strategy to combine structure-guided computational design, iterative site saturation mutagenesis, and yeast two-hybrid system (Y2H)-based phenotypic screening to engineer novel and orthogonal interactions between synthetic ligands and human estrogen receptor α (hERα) for the development of novel gene switches.

KW - Computational design

KW - Directed evolution

KW - Gene switch

KW - Protein-ligand interaction

UR - http://www.scopus.com/inward/record.url?scp=84964284169&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84964284169&partnerID=8YFLogxK

U2 - 10.1007/978-1-4939-3569-7_8

DO - 10.1007/978-1-4939-3569-7_8

M3 - Chapter

C2 - 27094289

AN - SCOPUS:84964284169

T3 - Methods in Molecular Biology

SP - 139

EP - 153

BT - Methods in Molecular Biology

PB - Humana Press Inc.

ER -