Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 57 (4), 376-382

Systems Approaches to Understanding and Designing Allosteric Proteins


Systems Approaches to Understanding and Designing Allosteric Proteins

Srivatsan Raman. Biochemistry.


The study of allostery has a central place in biology because of the myriad roles of allosteric proteins in cellular function. As technologies for probing the spatiotemporal resolution of biomolecules have become increasingly sophisticated, so has our understanding of the diverse structural and molecular mechanisms of allosteric proteins. Studies have shown that the allosteric signal is transmitted a through a network of residue-residue interactions connecting distal sites on a protein. Linking structural and dynamical changes to the functional role of individual residues will give a more complete molecular view of allostery. In this work, we highlight new mutational technologies that enable a systems-level, quantitative description of allostery that dissect the role of individual residues through large-scale functional screens. A molecular model for predicting allosteric hot spots can be developed by applying statistical tools on the resulting large sequence-structure-function data sets. Design of allosteric proteins with new function is essential for engineering biological systems. Previous design efforts demonstrate that the allosteric network is a powerful functional constraint in the design of novel or enhanced allosteric proteins. We discuss how a priori knowledge of an allosteric network could improve rational design by facilitating better navigation of the design space. Understanding the molecular "rules" governing allostery would elucidate the molecular basis of dysfunction in disease-associated allosteric proteins, provide a means for designing tailored therapeutics, and enable the design of new sensors and enzymes for synthetic biology.

Similar articles

See all similar articles

Cited by 1 PubMed Central articles

  • Protein Ensembles Link Genotype to Phenotype
    R Nussinov et al. PLoS Comput Biol 15 (6), e1006648. PMID 31220071. - Review
    Classically, phenotype is what is observed, and genotype is the genetic makeup. Statistical studies aim to project phenotypic likelihoods of genotypic patterns. The tradi …

Publication types


LinkOut - more resources