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Catalytic Role of Dehydrons in Soluble Proteins: Biological Chemistry of Frustrated Interfacial Water

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Book cover Physics at the Biomolecular Interface

Part of the book series: Soft and Biological Matter ((SOBIMA))

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Abstract

This chapter unravels the catalytic role of dehydrons at biomolecular interfaces. It prompts a significant revision of the mechanisms of biological chemistry to encompass the chemical functionality of frustrated interfacial water. We first establish the chemical basicity of interfacial water frustrated in its hydrogen-bonding opportunities due to partial confinement at sub-nanoscale structural defects (dehydrons). Through the functionalization of vicinal water, the dehydron is shown to be an enabler and promoter of enzymatic activity. Through multiple steering molecular dynamics with a pulling coordinate spanning the proton-transference trajectory, we show that the vast majority of transesterification reactions, ubiquitous in biological chemistry, are actually enabled by nearby dehydrons that deprotonate the pro-nucleophiles that may potentially intervene in such reactions. The theoretical results are validated against experimentally measured pKa decreases at functional sites and by experimental corroboration of the aberrant deregulation of catalytic activity arising from dehydron-creating mutations.

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Authors and Affiliations

  1. National Research Council (CONICET), Buenos Aires, Argentina

    Ariel Fernández (Former Hasselmann Professor of Engineering)

  2. Rice University, Houston, USA

    Ariel Fernández (Former Hasselmann Professor of Engineering)

Authors
  1. Ariel Fernández
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Fernández, A. (2016). Catalytic Role of Dehydrons in Soluble Proteins: Biological Chemistry of Frustrated Interfacial Water. In: Physics at the Biomolecular Interface. Soft and Biological Matter. Springer, Cham. https://doi.org/10.1007/978-3-319-30852-4_7

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