Computational design of receptor and sensor proteins with novel functions

@article{Looger2003ComputationalDO,
  title={Computational design of receptor and sensor proteins with novel functions},
  author={Loren L. Looger and Mary A. Dwyer and James Jefferson Smith and Homme W. Hellinga},
  journal={Nature},
  year={2003},
  volume={423},
  pages={185-190}
}
The formation of complexes between proteins and ligands is fundamental to biological processes at the molecular level. Manipulation of molecular recognition between ligands and proteins is therefore important for basic biological studies and has many biotechnological applications, including the construction of enzymes, biosensors, genetic circuits, signal transduction pathways and chiral separations. The systematic manipulation of binding sites remains a major challenge. Computational design… 
Genetically Engineered Proteins as Recognition Receptors
TLDR
The combination of screening libraries and utilizing computational tools is likely to provide the greatest progress in the future of biosensor design.
Protein Engineering for Biosensor Development Abstract Protein Engineering for Biosensor Development
TLDR
This work describes the application of protein engineering techniques to address three aspects in the design of protein-based biosensors; the transduction of binding into an observable, the manipulation of affinities, and the diversification of specificities.
Computational design of a Zn2+ receptor that controls bacterial gene expression
TLDR
These experiments demonstrate that biological systems can be manipulated with computationally designed proteins that have drastically altered ligand-binding specificities, thereby extending the repertoire of genetic control by extracellular signals.
Molecular recognition with designed peptides and proteins.
Analysis of ligand binding to a ribose biosensor using site‐directed mutagenesis and fluorescence spectroscopy
TLDR
The outcome of site‐directed mutagenesis on the Escherichia coli ribose binding protein (RBP) is investigated to help create more stable biosensors and optimize signal transduction properties for a variety of important analytes.
Protein and RNA engineering to customize microbial molecular reporting
TLDR
Recent advances in engineering small‐molecule recognition by proteins and RNA and in coupling in vivo ligand binding to reporter‐gene expression or to allosteric activation of a protein conferring a detectable phenotype are reviewed.
Ribose-Binding Protein Mutants With Improved Interaction Towards the Non-natural Ligand 1,3-Cyclohexanediol
TLDR
The results demonstrate that combinations of ligand-binding-pocket redesign and randomized mutagenesis can indeed lead to the selection and recovery of periplasmic-binding protein mutants with non-natural compound recognition.
Subcellular Localization Defects Characterize Ribose-Binding Mutant Proteins with New Ligand Properties in Escherichia coli
TLDR
Study of ribose-binding protein in Escherichia coli discovered that designed variants have defects in their proper localization in the cell, which can impair appropriate sensor signaling, and indicates that functional sensing capacity of PBPs cannot be obtained solely through computational design of the ligand-binding pocket but must take other properties of the protein into account, which are currently very difficult to predict.
Fluorescent Biosensors for Protein Interactions and Drug Discovery
TLDR
Fluorescent biosensors based in site-specific fluorescent labeling, as a result of combining the chemical attachment by site-directed mutagenesis and/ or manipulation of genetic code are focused on.
1 Fluorescent Biosensors for Protein Interactions and Drug Discovery
TLDR
Fluorescent biosensors based in site-specific fluorescent labeling, as a result of combining the chemical attachment by site-directed mutagenesis and/ or manipulation of genetic code are focused on.
...
...

References

SHOWING 1-10 OF 62 REFERENCES
Construction of a fluorescent biosensor family
TLDR
The facility of designing optical biosensors based on fluorophore conjugates using 8 environmentally sensitive fluorophores and 11 bPBPs specific for diverse ligands, including sugars, amino acids, anions, cations, and dipeptides is demonstrated.
Unnatural ligands for engineered proteins: new tools for chemical genetics.
TLDR
A newly developed approach to discovery of small molecule inhibitors/activators that relies on protein engineering and chemical synthesis has yielded powerful tools for the study of a wide variety of proteins involved in signal transduction.
Enzyme-like proteins by computational design
  • D. Bolon, S. L. Mayo
  • Biology, Chemistry
    Proceedings of the National Academy of Sciences of the United States of America
  • 2001
TLDR
The development and initial experimental validation of a computational design procedure aimed at generating enzyme-like protein catalysts called “protozymes” are reported, suggesting a possible mechanism for examining the relationships between protein fold and the evolvability of protein function.
Structural, functional, and evolutionary relationships among extracellular solute-binding receptors of bacteria.
TLDR
The occurrence of two distinct classes of bacterial cytoplasmic repressor proteins which are homologous to two different clusters of periplasmic binding proteins suggests that the gene-splicing events which allowed functional conversion of these proteins with retention of domain structure have occurred repeatedly during evolutionary history.
Transmembrane signalling by a hybrid protein: communication from the domain of chemoreceptor Trg that recognizes sugar-binding proteins to the kinase/phosphatase domain of osmosensor EnvZ
TLDR
The data indicate a common mechanism of transmembrane signal transduction by chemoreceptors and EnvZ, and functional coupling of sugar-binding protein recognition to kinase/phosphatase activity indicates shared features of intramolecular signalling in the two parent proteins.
Converting a maltose receptor into a nascent binuclear copper oxygenase by computational design.
TLDR
It is postulate that the equilibrium between the open and closed conformations of MBP allows species with variable Cu-Cu distances to form, and that such species can bind ligands in geometries that are not observed in natural type III centers.
Refined 1.89-A structure of the histidine-binding protein complexed with histidine and its relationship with many other active transport/chemosensory proteins.
TLDR
Elucidation of the HBP structure brings a total of eight different binding proteins structures determined in the laboratory, including those with specificities for monosaccharides, maltodextrins (linear and cyclic), aliphatic amino acids, and inorganic oxyanions, which provide understanding of molecular recognition of a variety of ligands at the atomic level and functional roles of the binding proteins.
Computer-aided design of a PDZ domain to recognize new target sequences
TLDR
Computer-aided protein design is used to produce mutant versions of a Class I PDZ domain that bind to novel Class I and Class II target sequences both in vitro and in vivo, thus providing an alternative to primary antibodies in western blotting, affinity chromatography and pull-down experiments.
...
...