Recent advances in employing molecular modelling to determine the specificity of glycan-binding proteins

Grant, Oliver C.; Woods, Robert J.

doi:10.1016/j.sbi.2014.07.001

Cited by 27 publications

(29 citation statements)

References 78 publications

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“…Overall, the different steps of binding, digestion, transport, and sensing combine into a series of filters that enhances specificity (Cuskin et al, 2012;Gilbert, Knox, & Boraston, 2013). Binding specificity of individual components is an active area of research (Glenwright et al, 2017;Grant & Woods, 2014;Ndeh et al, 2017;Tauzin et al, 2016).…”

Section: Receptor Diversity and Specificitymentioning

confidence: 99%

Receptor uptake arrays for vitamin B₁₂, siderophores, and glycans shape bacterial communities

Frank

2017

Ecology and Evolution

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Molecular variants of vitamin B12, siderophores, and glycans occur. To take up variant forms, bacteria may express an array of receptors. The gut microbe Bacteroides thetaiotaomicron has three different receptors to take up variants of vitamin B12 and 88 receptors to take up various glycans. The design of receptor arrays reflects key processes that shape cellular evolution. Competition may focus each species on a subset of the available nutrient diversity. Some gut bacteria can take up only a narrow range of carbohydrates, whereas species such as B. thetaiotaomicron can digest many different complex glycans. Comparison of different nutrients, habitats, and genomes provides opportunity to test hypotheses about the breadth of receptor arrays. Another important process concerns fluctuations in nutrient availability. Such fluctuations enhance the value of cellular sensors, which gain information about environmental availability and adjust receptor deployment. Bacteria often adjust receptor expression in response to fluctuations of particular carbohydrate food sources. Some species may adjust expression of uptake receptors for specific siderophores. How do cells use sensor information to control the response to fluctuations? This question about regulatory wiring relates to problems that arise in control theory and artificial intelligence. Control theory clarifies how to analyze environmental fluctuations in relation to the design of sensors and response systems. Recent advances in deep learning studies of artificial intelligence focus on the architecture of regulatory wiring and the ways in which complex control networks represent and classify environmental states. I emphasize the similar design problems that arise in cellular evolution, control theory, and artificial intelligence. I connect those broad conceptual aspects to many testable hypotheses for bacterial uptake of vitamin B12, siderophores, and glycans.

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Section: Receptor Diversity and Specificitymentioning

confidence: 99%

Receptor uptake arrays for vitamin B₁₂, siderophores, and glycans shape bacterial communities

Frank

2017

Ecology and Evolution

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“…Overall, the different steps of binding, digestion, transport, and sensing combine into a series of filters that enhances specificity 55,56 . Binding specificity of individual components is an active area of research 50,[57][58][59] .…”

Section: Receptor Diversity and Specificitymentioning

confidence: 99%

Receptor uptake arrays for vitamin B₁₂, siderophores and glycans shape bacterial communities

Frank

2017

Preprint

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Control theory clarifies how to analyze environmental fluctuations in relation to the design of sensors and response systems. Recent advances in deep learning studies of artificial intelligence focus on the architecture of regulatory wiring and the ways in which complex control networks represent and classify environmental states. I emphasize the similar design problems that arise in cellular evolution, control theory, and artificial intelligence. I connect those broad conceptual aspects to many testable hypotheses for bacterial uptake of vitamin B 12 , siderophores, and glycans. K E Y W O R D Scontrol theory, corrinoids, deep learning, microbiome, phenotypic plasticity, public goods, Plastic response requires sensor arrays to perceive availability.Environmental perception must then be transduced through a regulatory network that integrates information and alters deployment of the receptor array. How do aspects of environmental fluctuation shape the evolutionary design of sensory perception and the regulatory control to achieve a conditional response?I discuss how perception, classification, and response through a network relate to recent breakthroughs in artificial intelligence, neural networks, and deep learning. Bacterial systems provide great opportunity to link conceptual aspects of evolutionary design and deep learning to hypotheses that can be tested by comparative genomics and by experimental laboratory studies.I synthesize aspects of receptor arrays for vitamin B 12 analogs, for siderophores, and for glycans. By considering these different cases together, deeper principles of receptor variety and specificity emerge.Here, I use the word "receptor" to include the various binding and transport processes that influence specificity and rate of uptake. Degnan, Barry, et al. (2014), estimate that the human microbiome contains more than 30 receptor families for uptake of B 12 -like corrinoid variants. Genomic analyses predict that a significant fraction of all bacteria and archaea require a corrinoid variant for growth, yet only a minority can produce corrinoids (Rodionov, Vitreschak, Mironov, & Gelfand, 2003;Zhang, Rodionov, Gelfand, & Gladyshev, 2009). Competition over corrinoid variants shapes the receptor arrays of individual species and the dynamics of bacterial communities.Siderophores are secreted molecules that bind free iron. Bacteria use siderophore receptors to take up the siderophore-iron complexes.Iron often sets a limiting resource for microbial growth. Thus, competitive and cooperative processes over siderophore uptake shape bacterial community dynamics (Chakraborty, Braun, Hantke, & Cornelis, 2013;Niehus, Picot, Oliveira, Mitri, & Foster, 2017;West, Diggle, Buckling, Gardner, & Griffin, 2007). Individual bacteria may secrete more than one type of siderophore, or none at all. Bacteria typically have uptake receptors tuned for their own secreted types. In addition, bacteria often express an array of siderophore uptake receptors for types produced by other species (Loper & Henkels, 1999). Bacte...

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“…5 Molecular docking aims to predict various modes of noncovalent interactions between a macromolecule and a ligand, ranking the results based on binding energies or scores. 6 In general, the energy functions employed in docking are a summation of contributions from various nonbonded interactions (i.e., electrostatics, van der Waals, hydrogen bonding, and hydrophobic interactions).…”

Section: Introductionmentioning

confidence: 99%

Vina-Carb: Improving Glycosidic Angles during Carbohydrate Docking

Nivedha

Thieker

Makeneni

et al. 2016

J. Chem. Theory Comput.

117

118

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Molecular docking programs are primarily designed to align rigid, drug-like fragments into the binding sites of macromolecules and frequently display poor performance when applied to flexible carbohydrate molecules. A critical source of flexibility within an oligosaccharide is the glycosidic linkages. Recently, Carbohydrate Intrinsic (CHI) energy functions were reported that attempt to quantify the glycosidic torsion angle preferences. In the present work, the CHI-energy functions have been incorporated into the AutoDock Vina (ADV) scoring function, subsequently termed Vina-Carb (VC). Two user-adjustable parameters have been introduced, namely, a CHI- energy weight term (chi_coeff) that affects the magnitude of the CHI-energy penalty and a CHI-cutoff term (chi_cutoff) that negates CHI-energy penalties below a specified value. A data set consisting of 101 protein–carbohydrate complexes and 29 apoprotein structures was used in the development and testing of VC, including antibodies, lectins, and carbohydrate binding modules. Accounting for the intramolecular energies of the glycosidic linkages in the oligosaccharides during docking led VC to produce acceptable structures within the top five ranked poses in 74% of the systems tested, compared to a success rate of 55% for ADV. An enzyme system was employed in order to illustrate the potential application of VC to proteins that may distort glycosidic linkages of carbohydrate ligands upon binding. VC represents a significant step toward accurately predicting the structures of protein–carbohydrate complexes. Furthermore, the described approach is conceptually applicable to any class of ligands that populate well-defined conformational states.

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Recent advances in employing molecular modelling to determine the specificity of glycan-binding proteins

Cited by 27 publications

References 78 publications

Receptor uptake arrays for vitamin B₁₂, siderophores, and glycans shape bacterial communities

Receptor uptake arrays for vitamin B₁₂, siderophores, and glycans shape bacterial communities

Receptor uptake arrays for vitamin B₁₂, siderophores and glycans shape bacterial communities

Vina-Carb: Improving Glycosidic Angles during Carbohydrate Docking

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Recent advances in employing molecular modelling to determine the specificity of glycan-binding proteins

Cited by 27 publications

References 78 publications

Receptor uptake arrays for vitamin B12, siderophores, and glycans shape bacterial communities

Receptor uptake arrays for vitamin B12, siderophores, and glycans shape bacterial communities

Receptor uptake arrays for vitamin B12, siderophores and glycans shape bacterial communities

Vina-Carb: Improving Glycosidic Angles during Carbohydrate Docking

Contact Info

Product

Resources

About

Receptor uptake arrays for vitamin B₁₂, siderophores, and glycans shape bacterial communities

Receptor uptake arrays for vitamin B₁₂, siderophores, and glycans shape bacterial communities

Receptor uptake arrays for vitamin B₁₂, siderophores and glycans shape bacterial communities