Empirical predictions of an intrinsically disordered protein theory approach to glycan/lectin reaction kinetics

Rodrick Wallace

doi:10.1038/npre.2012.6752.1

Abstract

AbstractNewly-developed methods from the theory of intrinsically disordered proteins can be applied to the flexible glycan structures that coat cellular surfaces and provide rich channels for biological information transmission. Extension of a mechanistic 'arm-in-sleeve' model via a nonrigid molecule symmetry analysis leads to expectation of empirical observation of punctuated 'spectral' classifications in glycan/lectin interaction, parameterized by an appropriate index of glycan frond length or other index of topological complexity, possibly requiring groupoid classifications analogous to quasicrystals.

Highlights

Flexible glycan fronds coat the cellular surface and provide a signaling base for a vast spectrum of interactions with other biological structures and entities, ranging from tissue partners to pathogens and parasites
The line of argument can be made more precise by invoking same kind of nonrigid molecule argument that Wallace (2011b, 2012b) has applied to intrinsically disordered proteins: we like to think of IDP and glycan/lectin reactions in classical terms, invoking such metaphors as ‘flycasting’ or ‘a snake slithering’, these are complicated processes of quantum chemistry that may benefit from more formal examination
An essential outcome of this approach is that the glycan symmetries, and their associated dynamics, should be highly punctuated in the parameter L that indexes final glycan topological form, and this effect should be observable

Summary

Introduction

Flexible glycan fronds coat the cellular surface and provide a signaling base for a vast spectrum of interactions with other biological structures and entities, ranging from tissue partners to pathogens and parasites. Wallace (2012a) has examined the reducto ad absurdum implied by application of Tlusty’s elegant rate distortion error code analysis in the context of so many fundamental building blocks, finding that the production of flexible glycan fronds at the cell surface must be regulated by sophisticated processes of chemical cognition. While evolutionary conservation is roughly in the order of genetic code > RNA sequences > primary protein sequence > metabolic pathways > cellular lipid composition > surface glycan structures, the information content, related to structural diversity, is in reverse order

Catalysis by mechanical flexibility

Nonrigid molecule theory

Extending the model