Diffuse ions coordinate dynamics in a ribonucleoprotein assembly

Mapping Intimacies ◽

10.1101/2021.06.25.448160 ◽

2021 ◽

Author(s):

Ailun Wang ◽

Mariana Levi ◽

Udayan Mohanty ◽

Paul Charles Whitford

Keyword(s):

Long Range ◽

Computational Techniques ◽

Direct Impact ◽

Effective Potentials ◽

Ionic Concentrations ◽

Functional Dynamics ◽

Bacterial Ribosome ◽

Ribonucleoprotein Assembly

Proper ionic concentrations are required for the functional dynamics of RNA and ribonucleoprotein (RNP) assemblies. While experimental and computational techniques have provided many insights into the properties of chelated ions, less is known about the structural/energetic contributions of diffuse ions. To address this, we present a model that is designed to identify the influence of diffuse ions on the dynamics of biomolecular assemblies. This model employs all-atom (non-H) resolution and explicit ions (monovalent and divalent), where effective potentials account for hydration effects. To benchmark the model, we show that it accurately predicts the number of excess Mg2+ ions for prototypical RNA systems. We then apply it to a bacterial ribosome and find that diffuse ions control the position of the extended L1 stalk region. The simulations also illustrate how diffuse ions facilitate long-range attraction between tRNA and the stalk region. Together, this analysis reveals the direct impact of diffuse ions on the dynamics of an RNP assembly.

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FcαRI binding at the IgA1 CH2–CH3 interface induces long-range conformational changes that are transmitted to the hinge region

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1807478115 ◽

2018 ◽

Vol 115 (38) ◽

pp. E8882-E8891 ◽

Cited By ~ 7

Author(s):

Monica T. Posgai ◽

Sam Tonddast-Navaei ◽

Manori Jayasinghe ◽

George M. Ibrahim ◽

George Stan ◽

...

Keyword(s):

Binding Site ◽

Long Range ◽

Conformational Changes ◽

Lectin Binding ◽

Coarse Grained ◽

Alanine Scanning Mutagenesis ◽

Long Distance ◽

Receptor Binding Site ◽

Binding Interface ◽

Functional Dynamics

IgA effector functions include proinflammatory immune responses triggered upon clustering of the IgA-specific receptor, FcαRI, by IgA immune complexes. FcαRI binds to the IgA1–Fc domain (Fcα) at the CH2–CH3 junction and, except for CH2 L257 and L258, all side-chain contacts are contributed by the CH3 domain. In this study, we used experimental and computational approaches to elucidate energetic and conformational aspects of FcαRI binding to IgA. The energetic contribution of each IgA residue in the binding interface was assessed by alanine-scanning mutagenesis and equilibrium surface plasmon resonance (SPR). As expected, hydrophobic residues central to the binding site have strong energetic contributions to the FcαRI:Fcα interaction. Surprisingly, individual mutation of CH2 residues L257 and L258, found at the periphery of the FcαRI binding site, dramatically reduced binding affinity. Comparison of antibody:receptor complexes involving IgA or its precursor IgY revealed a conserved receptor binding site at the CH2–CH3 junction (or its equivalent). Given the importance of residues near the CH2–CH3 junction, we used coarse-grained Langevin dynamics simulations to understand the functional dynamics in Fcα. Our simulations indicate that FcαRI binding, either in an asymmetric (1:1) or symmetric (2:1) complex with Fcα, propagated long-range conformational changes across the Fc domains, potentially impacting the hinge and Fab regions. Subsequent SPR experiments confirmed that FcαRI binding to the Fcα CH2–CH3 junction altered the kinetics of HAA lectin binding at the IgA1 hinge. Receptor-induced long-distance conformational transitions have important implications for the interaction of aberrantly glycosylated IgA1 with anti-glycan autoantibodies in IgA nephropathy.

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Pattern formation and self-assembly driven by competing interactions

Soft Matter ◽

10.1039/c7sm02125a ◽

2017 ◽

Vol 13 (48) ◽

pp. 9259-9272 ◽

Cited By ~ 16

Author(s):

Davide Pini ◽

Alberto Parola

Keyword(s):

Pattern Formation ◽

Long Range ◽

Self Assembly ◽

Short Range ◽

Competing Interactions ◽

Effective Potentials ◽

Simple Mechanism ◽

Colloidal Fluids

Colloidal fluids interacting via effective potentials which are attractive at the short range and repulsive at the long range have long been raising considerable attention because such an instance provides a simple mechanism leading to pattern formation even for isotropic interactions.

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Coarse-Grained Models Reveal Functional Dynamics – II. Molecular Dynamics Simulation at the Coarse-Grained Level – Theories and Biological Applications

Bioinformatics and Biology Insights ◽

10.4137/bbi.s459 ◽

2008 ◽

Vol 2 ◽

pp. BBI.S459 ◽

Cited By ~ 9

Author(s):

Choon-Peng Chng ◽

Lee-Wei Yang

Keyword(s):

Molecular Dynamics ◽

Molecular Conformation ◽

Conformational Dynamics ◽

Dynamics Simulation ◽

Coarse Grained ◽

Time Step ◽

Effective Potentials ◽

Functional Dynamics ◽

Indispensable Tool ◽

Selection Of

Molecular dynamics (MD) simulation has remained the most indispensable tool in studying equilibrium/non-equilibrium conformational dynamics since its advent 30 years ago. With advances in spectroscopy accompanying solved biocomplexes in growing sizes, sampling their dynamics that occur at biologically interesting spatial/temporal scales becomes computationally intractable; this motivated the use of coarse-grained (CG) approaches. CG-MD models are used to study folding and conformational transitions in reduced resolution and can employ enlarged time steps due to the a bsence of some of the fastest motions in the system. The Boltzmann-Inversion technique, heavily used in parameterizing these models, provides a smoothed-out effective potential on which molecular conformation evolves at a faster pace thus stretching simulations into tens of microseconds. As a result, a complete catalytic cycle of HIV-1 protease or the assembly of lipid-protein mixtures could be investigated by CG-MD to gain biological insights. In this review, we survey the theories developed in recent years, which are categorized into Folding-based and Molecular-Mechanics-based. In addition, physical bases in the selection of CG beads/time-step, the choice of effective potentials, representation of solvent, and restoration of molecular representations back to their atomic details are systematically discussed.

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