Low-Frequency Harmonic Perturbations Drive Protein Conformational Changes

Protein dynamics has been investigated since almost half a century, as it is believed to constitute the fundamental connection between structure and function. Elastic network models (ENMs) have been widely used to predict protein dynamics, flexibility and the biological mechanism, from which remarkable results have been found regarding the prediction of protein conformational changes. Starting from the knowledge of the reference structure only, these conformational changes have been usually predicted either by looking at the individual mode shapes of vibrations (i.e., by considering the free vibrations of the ENM) or by applying static perturbations to the protein network (i.e., by considering a linear response theory). In this paper, we put together the two previous approaches and evaluate the complete protein response under the application of dynamic perturbations. Harmonic forces with random directions are applied to the protein ENM, which are meant to simulate the single frequency-dependent components of the collisions of the surrounding particles, and the protein response is computed by solving the dynamic equations in the underdamped regime, where mass, viscous damping and elastic stiffness contributions are explicitly taken into account. The obtained motion is investigated both in the coordinate space and in the sub-space of principal components (PCs). The results show that the application of perturbations in the low-frequency range is able to drive the protein conformational change, leading to remarkably high values of direction similarity. Eventually, this suggests that protein conformational change might be triggered by external collisions and favored by the inherent low-frequency dynamics of the protein structure.

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Anti-peptide antibodies detect steps in a protein conformational change: low-pH activation of the influenza virus hemagglutinin.

The Journal of Cell Biology ◽

10.1083/jcb.105.6.2887 ◽

1987 ◽

Vol 105 (6) ◽

pp. 2887-2896 ◽

Cited By ~ 206

Author(s):

J M White ◽

I A Wilson

Keyword(s):

Influenza Virus ◽

Membrane Fusion ◽

Conformational Change ◽

Conformational Changes ◽

Three Dimensional ◽

Low Ph ◽

Protein Conformational Changes ◽

Influenza Virus Hemagglutinin ◽

Protein Conformational Change ◽

Peptide Antibodies

At low pH, the hemagglutinin (HA) of influenza virus undergoes an irreversible conformational change that potentiates its essential membrane fusion function. We have probed the details of this conformational change using a panel of 14 anti-HA-peptide antibodies. Whereas some antibodies reacted equally well with both the neutral and low-pH HA conformations, others reacted to a significantly greater extent with the low-pH form. The locations of the peptides recognized by the latter antibodies in the three-dimensional HA structure indicated regions of the protein that change in response to low pH. Moreover, kinetic experiments suggested steps in the conformational change. In addition to their relevance to membrane fusion, our results show that anti-peptide antibodies can be used to study some types of biologically important protein conformational changes.

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Protein Conformational Changes and Low-Frequency Vibrational Modes: A Similarity Analysis

Mechanics of Biological Systems and Materials & Micro-and Nanomechanics, Volume 4 - Conference Proceedings of the Society for Experimental Mechanics Series ◽

10.1007/978-3-030-30013-5_2 ◽

2019 ◽

pp. 7-10 ◽

Cited By ~ 1

Author(s):

Domenico Scaramozzino ◽

Giuseppe Lacidogna ◽

Alberto Carpinteri

Keyword(s):

Conformational Changes ◽

Low Frequency ◽

Similarity Analysis ◽

Vibrational Modes ◽

Protein Conformational Changes

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Probing Ca2+-induced conformational change of calmodulin with gold nanoparticle-decorated single-walled carbon nanotube field-effect transistors

Nanoscale ◽

10.1039/c9nr03132d ◽

2019 ◽

Vol 11 (28) ◽

pp. 13397-13406 ◽

Cited By ~ 3

Author(s):

Wenting Shao ◽

Seth C. Burkert ◽

David L. White ◽

Valerie L. Scott ◽

Jianfu Ding ◽

...

Keyword(s):

Carbon Nanotube ◽

Gold Nanoparticle ◽

Conformational Change ◽

Conformational Changes ◽

Field Effect ◽

Field Effect Transistors ◽

Metal Nanoparticle ◽

Single Walled Carbon Nanotube ◽

Protein Conformational Changes ◽

Carbon Nanotube Fet

Nanoelectronic detection of ion-induced protein conformational changes with metal nanoparticle-decorated carbon nanotube FET.

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A MOLECULAR MECHANISM FOR THE DITHI0THREIT0L-MEDIAT5D PLATELET AGGREGATION

10.1055/s-0038-1644495 ◽

1987 ◽

Author(s):

Moideen P Jamaluddin ◽

C Sreedevi ◽

Ancy Thomas ◽

Lissy K Krishnan

Keyword(s):

Platelet Aggregation ◽

Conformational Change ◽

Conformational Changes ◽

Actin Polymerization ◽

Spectral Measurements ◽

Stimulus Response ◽

Excluded Volume Effects ◽

The Press ◽

Protein Conformational Change ◽

Biochemical Mechanisms

Biochemical mechanisms of stimulus response coupling is an intricate problem in platelet biochemistry. Recently we obtained evidence that support the view that conformational changes of an (unsaturated fatty acid – and U46619-binding) haemoprotein induced by the binding of arachidonic acid, H2O2 or PGH2 liberated in apparently different platelet compartments in response to different stimuli could constitute a mechanism (L.K. Krishnan … M.P. Jamaluddin, FEBS Lett, in the press). We investigated the effect of dithiothreitol (DTT), a platelet agonist whose mechanism of action is unknown, on the purified haemoprotein. DTT was found by spectral measurements and gelfiltration experiments to bring about a slow time-dependent conformational .change and oligomerization of the protein concomitantly with its oxidation. Oxidised DTT (trans-4,5-dihy-droxy-1,2-dithiane) was found to induce a similar conformational change by binding to the protein (halfsaturation cancn. 2 mM). Oligomerization changed the charge characteristics of the protein, from net positive to net negative, ait pH 7.4. Protein-protein association is associated with large volume increases. Excluded volume effects and changes in charge distribution at the side of protein conformational change could trigger actin polymerization, pseudopod formation and aggregation, modulated by protein phosphorylation and Ca2+ concentration. In conformity with these ideas oxidized DTT near its half-maximal saturation concentration for the protein, was found to aggregate gelfiltered calf platelets. Presumably it functions as a thioanalogue of PGH2. Oxidized glutathione or oxidized 2-mercaptoethanol could also bring about protein conformational change and platelet aggregation.

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FTIR Spectroscopy Detects Intermolecular β-Sheet Formation Above the High Temperature Tm for Two Monoclonal Antibodies

The Protein Journal ◽

10.1007/s10930-020-09907-y ◽

2020 ◽

Vol 39 (4) ◽

pp. 318-327

Author(s):

Garrett Baird ◽

Chris Farrell ◽

Jason Cheung ◽

Andrew Semple ◽

Jeffery Blue ◽

...

Keyword(s):

Monoclonal Antibodies ◽

Protein Aggregation ◽

Ftir Spectroscopy ◽

Conformational Change ◽

Conformational Changes ◽

Sucrose Concentration ◽

Transmission Mode ◽

Protein Conformational Change ◽

Β Sheets ◽

The Impact

AbstractThe temperature-dependent secondary structure of two monoclonal IgG antibodies, anti-IGF1R and anti-TSLP, were examined by transmission mode Fourier Transform Infrared (FTIR) spectroscopy. Anti-IGF1R and anti-TSLP are IgG monoclonal antibodies (mAbs) directed against human Insulin-like Growth Factor 1 Receptor for anti-tumor activity and Thymic Stromal Lymphopoietin cytokine for anti-asthma activity, respectively. Differential scanning calorimetry (DSC) clearly indicates both antibodies in their base formulations have a lower temperature protein conformational change near 70 °C (Tm1) and a higher temperature protein conformational change near 85 °C (Tm2). Thermal scanning dynamic light scatting (TS-DLS) indicates a significant particle size increase for both antibodies near Tm2 suggesting a high level of protein aggregation. The nature of these protein conformational changes associated with increasing the formulation temperature and decreasing sucrose concentration were identified by transmission mode FTIR and second derivative FTIR spectroscopy of temperature controlled aqueous solutions of both monoclonal antibodies. The transition from intra-molecular β sheets to inter-molecular β sheets was clearly captured for both monoclonal antibodies using FTIR spectroscopy. Finally, FTIR Spectroscopy was able to show the impact of a common excipient such as sucrose on the stability of each monoclonal antibody, further demonstrating the usefulness of FTIR spectroscopy for studying protein aggregation and formulation effects.

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Calculation-and-experimental estimation of the role of the frequency ratio in changing the endurance at two-frequency deformation modes

Industrial laboratory Diagnostics of materials ◽

10.26896/1028-6861-2019-85-1-i-64-71 ◽

2019 ◽

Vol 85 (1(I)) ◽

pp. 64-71 ◽

Cited By ~ 1

Author(s):

M. M. Gadenin

Keyword(s):

High Frequency ◽

Experimental Studies ◽

Low Frequency ◽

Reduction Factor ◽

Single Frequency ◽

Cyclic Loads ◽

Small Ratio ◽

Harmonic Components ◽

Deformation Modes

The cycle configuration at two-frequency loading regimes depends on the number of parameters including the absolute values of the frequencies and amplitudes of the low-frequency and high-frequency loads added during this mode, the ratio of their frequencies and amplitudes, as well as the phase shift between these harmonic components, the latter having a significant effect only with a small ratio of frequencies. Presence of such two-frequency regimes or service loading conditions for parts of machines and structures schematized by them can significantly reduce their endurance. Using the results of experimental studies of changes in the endurance of a two-frequency loading of specimens of cyclically stable, cyclically softened and cyclically hardened steels under rigid conditions we have shown that decrease in the endurance under the aforementioned conditions depends on the ratio of frequencies and amplitudes of operation low-frequency low-cycle and high-frequency vibration stresses, and, moreover, the higher the level of the ratios of amplitudes and frequencies of those stacked harmonic processes of loading the greater the effect. It is shown that estimation of such a decrease in the endurance compared to a single frequency loading equal in the total stress (strains) amplitudes can be carried out using an exponential expression coupling those endurances through a parameter (reduction factor) containing the ratio of frequencies and amplitudes of operation cyclic loads and characteristic of the material. The reduction is illustrated by a set of calculation-experimental curves on the corresponding diagrams for each of the considered types of materials and compared with the experimental data.

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