Insights in the structural understanding of amyloidogenicity and mutation-led conformational dynamics of amyloid beta (Aβ) through molecular dynamics simulations and principal component analysis

Raghavan, Sriram; Iqbal, Saleem; Ayyadurai, Niraikulam; Gunasekaran, Krishnasamy

doi:10.1080/07391102.2021.1871955

Cited by 9 publications

(8 citation statements)

References 41 publications

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“…PCA was computed on the backbone (Cα) atoms of the amino acid residues to assess the structural alterations or conformational changes present in the secondary structure of HSA in the presence and absence of the dye. PCA serves as a potent analytical tool, facilitating the visualization of synchronized atomic displacements occurring within macromolecules during MD trajectories 50,65–68 . Significantly, the initial three Eigenvectors collectively elucidated around 60% of the dynamic motions 50–52 .…”

Section: Resultsmentioning

confidence: 99%

“…PCA serves as a potent analytical tool, facilitating the visualization of synchronized atomic displacements occurring within macromolecules during MD trajectories. 50,[65][66][67][68] Significantly, the initial three Eigenvectors collectively elucidated around 60% of the dynamic motions. [50][51][52] The overlay of primary principal components on a 2D plane provides a lucid representation of atomic displacement patterns (Figure 10).…”

Section: Principal Component Analysismentioning

confidence: 99%

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Biophysical and structural characterization of tetramethrin serum protein complex and its toxicological implications

Singh,

Gopi,

Rani

et al. 2024

J of Molecular Recognition

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Tetramethrin (TMT) is a commonly used insecticide and has a carcinogenic and neurodegenerative effect on humans. The binding mechanism and toxicological implications of TMT to human serum albumin (HSA) were examined in this study employing a combination of biophysical and computational methods indicating moderate binding affinity and potential hepato and renal toxicity. Fluorescence quenching experiments showed that TMT binds to HSA with a moderate affinity, and the binding process was spontaneous and predominantly enthalpy‐driven. Circular dichroism spectroscopy revealed that TMT binding did not induce any significant conformational changes in HSA, resulting in no changes in its alpha‐helix content. The binding site and modalities of TMT interactions with HSA as computed by molecular docking and molecular dynamics simulations revealed that it binds to Sudlow site II of HSA via hydrophobic interactions through its dimethylcyclopropane carboxylate methyl propanyl group. The structural dynamics of TMT induce proper fit into the binding site creating increased and stabilizing interactions. Additionally, molecular mechanics–Poisson Boltzmann surface area calculations also indicated that non‐polar and van der Waals were found to be the major contributors to the high binding free energy of the complex. Quantum mechanics (QM) revealed the conformational energies of the binding confirmation and the degree of deviation from the global minimum energy conformation of TMT. The results of this study provide a comprehensive understanding of the binding mechanism of TMT with HSA, which is important for evaluating the toxicity of this insecticide in humans.

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Section: Resultsmentioning

confidence: 99%

Section: Principal Component Analysismentioning

confidence: 99%

Biophysical and structural characterization of tetramethrin serum protein complex and its toxicological implications

Singh,

Gopi,

Rani

et al. 2024

J of Molecular Recognition

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“…Principal component analysis (PCA) was performed in molecular dynamics simulation (MD simulation), in which principle components (PCs) are eigenvectors that specify the motion's direction and eigenvalues specify the amount of residual motion. The PCA was conducted using Gromacs 2021.5 for the complexes constructed by multi-epitope vaccines with B7-1, B7-2, TLR-2, TLR-4, and projected PC1 and PC2 into two dimensions 51 .…”

Section: Methodsmentioning

confidence: 99%

Design of a novel multiepitope vaccine against Chlamydia pneumoniae using the extracellular protein as a target

Guo,

Pan,

Sun

et al. 2023

Sci Rep

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Chlamydia pneumoniae (C. pneumoniae) infection in humans is universal and causes various respiratory infectious diseases, making a safe and effective preventive vaccine essential. In this study, a multi-epitope vaccine with CTLA-4 extracellular structure was constructed by an immunoinformatics approach. Since MOMP protein is the major extracellular protein in C. pneumoniae and has good immunogenicity and high conservation, we selected the MOMP protein of C. pneumoniae as the antigen target, predicted the T and B cell epitopes of the MOMP protein and then connected the CTLA-4 extracellular structure with the predicted dominant epitopes by various linkers to construct a multi-epitope vaccine. The biochemical characterization of the multi-epitope vaccine showed its immunogenicity and anti-allergic properties. The tertiary structure of this vaccine, along with molecular docking, molecular dynamics simulation, and principal component analysis, showed that the multi-epitope vaccine structure interacted with B7 (B7-1, B7-2) and toll-like receptors (TLR-2, TLR-4). Ultimately, the vaccine was cloned and effectively expressed in silico on an insect baculovirus expression vector (pFastBac1). These analyses showed that the designed vaccine could potentially target antigen-presenting cells and was immune to C. pneumoniae, which provided novel strategies for developing the vaccine.

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“…PCA can identify important patterns of interacting systems generated by MD simulations. In MD, the principal components (PCs) are the eigenvectors that determine the direction of motion, and the eigenvalues represent the degree of residual motion 49 . In this study, the Gromacs 2021.4 was used to analyze the trajectory of the simulation, and the most critical principal component 1 (PC1) and principal component 2 (PC2) were projected into 2 dimensions.…”

Section: Methodsmentioning

confidence: 99%

Immmunoinformatics‐based design of a multi‐epitope vaccine with CTLA‐4 extracellular domain to combat Helicobacter pylori

Zhu

et al. 2022

The FASEB Journal

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In view of the high infection rate of Helicobacter pylori, a safe and effective vaccine is urgently needed. Recent trends in vaccine design have shifted toward safe and specific epitope‐based vaccines. In this study, by using different immunoinformatics approaches, a total of eight linear B cell epitopes, four HTL and three CTL epitopes of FlaA and UreB proteins of H. pylori G27 strain were screened out, we also predicted the conformational epitopes of the two proteins. Then, the dominant epitopes were sequentially linked by appropriate linkers, and the cytotoxic T lymphocyte–associated antigen 4 extracellular domain was attached to the N‐terminal of the epitope sequence. Meanwhile, molecular docking, molecular dynamics simulations and principal component analysis were performed to show that the multi‐epitope vaccine structure had strong interactions with B7 (B7‐1, B7‐2) and Toll‐like receptors (TLR‐2, ‐4). Eventually, the effectiveness of the vaccine was validated using in silico cloning. These analyses suggested that the designed vaccine could target antigen‐presenting cells and had high potency against H. pylori, which could provide a reference for the future development of efficient H. pylori vaccines.

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Insights in the structural understanding of amyloidogenicity and mutation-led conformational dynamics of amyloid beta (Aβ) through molecular dynamics simulations and principal component analysis

Cited by 9 publications

References 41 publications

Biophysical and structural characterization of tetramethrin serum protein complex and its toxicological implications

Biophysical and structural characterization of tetramethrin serum protein complex and its toxicological implications

Design of a novel multiepitope vaccine against Chlamydia pneumoniae using the extracellular protein as a target

Immmunoinformatics‐based design of a multi‐epitope vaccine with CTLA‐4 extracellular domain to combat Helicobacter pylori

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