Combined and Iterative Use of Computational Design and Directed Evolution for Protein-Ligand Binding Design.
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.
Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
Meng
M
Wang
Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA. zhao5@illinois.edu.|Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA. zhao5@illinois.edu.|Department of Chemistry, and Bioengineering, and Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA. zhao5@illinois.edu.|215 Rogers Adams Lab, Box C-3 600 S. Matthews Ave., Urbana, IL, 61801, USA. zhao5@illinois.edu.
Huimin
H
Zhao
D019020:Directed Molecular Evolution; D008024:Ligands; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*
D008024:Ligands; D011506:Proteins
Computational design; Directed evolution; Gene switch; Protein–ligand interaction