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Protein as evolvable functionally constrained amorphous matter

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Abstract

We explore current ideas around the representation of a protein as an amorphous material, in turn represented by an abstract graph \(\mathcal{G}\) with edges weighted by elastic stiffnesses. By embedding this graph in physical space, we can map every graph to a spectrum of conformational fluctuations and responses (as a result of, say, ligand-binding). This sets up a ‘genotype–phenotype’ map, which we use to evolve the amorphous material to select for fitness. Using this, we study the emergence of allosteric interaction, hinge joint, crack formation and a slide bolt in functional proteins such as adenylate kinase, HSP90, calmodulin and GPCR proteins. We find that these emergent features are associated with specific geometries and mode spectra of floppy or liquid-like regions. Our analysis provides insight into understanding the architectural demands on a protein that enable a prescribed function and its stability to mutations.

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Acknowledgements

It is a pleasure to present this article as part of the thematic issue titled "Emergent dynamics of biological networks" in honor of Prof. Somdatta Sinha. At a time when Theoretical Biology was not very popular in India, it was scientists like Somdatta who bravely kept the intellectual flame burning. Somdatta continues to be a gracious mentor to the younger generation of biophysicists.

MR acknowledges support from the Department of Atomic Energy (India), under project no. RTI4006, and the Simons Foundation (Grant No. 287975).

MR and SS acknowledge the award of JC Bose Fellowships, JCB/2018/000030 and JBR/2020/000015, respectively, from SERB-DST, India. AS thanks the Department of Science and Technology, India, for the early career reward (ECR) grant. MT acknowledges the research fellowship from the Department of Biotechnology, India. This research was also supported by the Department of Biotechnology, Government of India, in the form of IISc-DBT partnership programme.

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Author notes

  1. Madhusmita Tripathy

    Present address: Eduard-Zintl-Institut für Anorganische und Physikalische Chemie, Technische Universität Darmstadt, 64287, Darmstadt, Germany

Authors and Affiliations

  1. Molecular Biophysics Unit, Indian Institute of Science, Bengaluru, 560012, India

    Madhusmita Tripathy & Anand Srivastava

  2. Theoretical Sciences Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bengaluru, 560064, India

    Srikanth Sastry

  3. Simons Centre for the Study of Living Machines, National Centre for Biological Sciences (TIFR), Bengaluru, 560065, India

    Madan Rao

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  1. Madhusmita Tripathy
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  2. Anand Srivastava
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Correspondence to Madan Rao.

Additional information

Corresponding editor: Susmita Roy

This article is part of the Topical Collection: Emergent dynamics of biological networks.

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Tripathy, M., Srivastava, A., Sastry, S. et al. Protein as evolvable functionally constrained amorphous matter. J Biosci 47, 73 (2022). https://doi.org/10.1007/s12038-022-00313-3

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  • DOI: https://doi.org/10.1007/s12038-022-00313-3

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