Investigation of structural stability and functionality of homodimeric gramicidin towards peptide‐based drug: a molecular simulation approach

Ganesan, P.; Rajasekaran, R.

doi:10.1002/jcb.27765

Cited by 12 publications

(7 citation statements)

References 64 publications

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“…Unlike nABP284, nABPD1 has a branched chain (SHHHRL), making the secondary structure of the new peptide more complex. We hypothesized that the stability of the new peptide would also benefit from this modification [ 27 , 28 ]. Due to their vigorous metabolism, the local microenvironment of solid malignant tumors is mostly acidic, and as a basic peptide, nABPD1 tends to accumulate in the acidic microenvironment of tumors [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Engineering a High-Affinity PD-1 Peptide for Optimized Immune Cell-Mediated Tumor Therapy

et al. 2022

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The purpose of this study was to optimize a peptide (nABP284) that binds to PD-1 by a computer-based protocol in order to increase its affinity. Then, this study aimed to determine the inhibitory effects of this peptide on cancer immune escape by coculturing improving cytokine-induced killer (ICIK) cells with cancer cells. Materials and MethodsnABP284 that binds to PD-1 was identified by phage display technology in our previous study.AutoDock and PyMOL were used to optimize the sequence of nABP284 to design a new peptide (nABPD1). Immunofluorescence was used to demonstrate that the peptides bound to PD-1. Surface plasmon resonance (SPR) was used to measure the binding affinity of the peptides. The blocking effect of the peptides on PD-1 was evaluated by a neutralization experiment with human recombinant PD-L1 protein. The inhibition of activated lymphocytes by cancer cells was simulated by coculturing of human acute T lymphocytic leukemia cells (Jurkat T cells) with human tongue squamous cell carcinoma cells (Cal27 cells). The anticancer activities were determined by coculturing ICIK cells with Cal27 cells in vitro. ResultsA high-affinity peptide (nABPD1, KD=11.9 nM) for PD-1 was obtained by optimizing the nABP284 peptide (KD=11.8 µM). nABPD1 showed better efficacy than nABP284 in terms of increasing the secretion of IL-2 by Jurkat T cells and enhancing the in vitro antitumor activity of ICIK cells. ConclusionnABPD1 possesses higher affinity for PD-1 than nABP284, which significantly enhances its ability to block the PD-1/PD-L1 interaction and to increase ICIK cell-mediated antitumor activity by armoring ICIK cells.

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Section: Discussionmentioning

confidence: 99%

Engineering a High-Affinity PD-1 Peptide for Optimized Immune Cell-Mediated Tumor Therapy

et al. 2022

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“…MD simulation is capable of identifying this information that can help us understand the detailed mechanism of the inhibition. Other than the corrosion field, MD simulation also offers numerous advantages in various sectors such as renewable energy generation, food technology, medicine, and pharmaceutical [15][16][17][18]. A broad list of reviews of MD simulation application for corrosion sector as well as other sectors had been published in the literature [14,[19][20][21][22].…”

Section: Introductionmentioning

confidence: 99%

An Overview of Molecular Dynamic Simulation for Corrosion Inhibition of Ferrous Metals

Haris

Sobri

Yusof

et al. 2020

Metals

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Molecular dynamics (MD) simulation is a powerful tool to study the molecular level working mechanism of corrosion inhibitors in mitigating corrosion. In the past decades, MD simulation has emerged as an instrument to investigate the interactions at the interface between the inhibitor molecule and the metal surface. Combined with experimental measurement, theoretical examination from MD simulation delivers useful information on the adsorption ability and orientation of the molecule on the surface. It relates the microscopic characteristics to the macroscopic properties which enables researchers to develop high performance inhibitors. Although there has been vast growth in the number of studies that use molecular dynamic evaluation, there is still lack of comprehensive review specifically for corrosion inhibition of organic inhibitors on ferrous metal in acidic solution. Much uncertainty still exists on the approaches and steps in performing MD simulation for corrosion system. This paper reviews the basic principle of MD simulation along with methods, selection of parameters, expected result such as adsorption energy, binding energy and inhibitor orientation, and recent publications in corrosion inhibition studies.

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“…However, Yoon et al reported that mutations which occurred far from the active site might be involved in altering the catalytic property by changing the protein folding and expression rate (Sheen et al, 2009;Rajendran and Sethumadhavan, 2013;Yoon et al, 2014;Yadon et al, 2017). Amino acid substitution of a protein's structure may result in drastic effects, especially on the binding pockets and its surroundings (Worth et al, 2009;Ganesan and Ramalingam, 2018) or they may have longranging effects (Kosloff and Kolodny, 2008). The second major cause behind PZA resistance is mutations in RpsA.…”

Section: Introductionmentioning

confidence: 99%

Gibbs Free Energy Calculation of Mutation in PncA and RpsA Associated With Pyrazinamide Resistance

Khan

Ali

Zeb³

et al. 2020

Front. Mol. Biosci.

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A central approach for better understanding the forces involved in maintaining protein structures is to investigate the protein folding and thermodynamic properties. The effect of the folding process is often disturbed in mutated states. To explore the dynamic properties behind mutations, molecular dynamic (MD) simulations have been widely performed, especially in unveiling the mechanism of drug failure behind mutation. When comparing wild type (WT) and mutants (MTs), the structural changes along with solvation free energy (SFE), and Gibbs free energy (GFE) are calculated after the MD simulation, to measure the effect of mutations on protein structure. Pyrazinamide (PZA) is one of the first-line drugs, effective against latent Mycobacterium tuberculosis isolates, affecting the global TB control program 2030. Resistance to this drug emerges due to mutations in pncA and rpsA genes, encoding pyrazinamidase (PZase) and ribosomal protein S1 (RpsA) respectively. The question of how the GFE may be a measure of PZase and RpsA stabilities, has been addressed in the current review. The GFE and SFE of MTs have been compared with WT, which were already found to be PZA-resistant. WT structures attained a more stable state in comparison with MTs. The physiological effect of a mutation in PZase and RpsA may be due to the difference in energies. This difference between WT and MTs, depicted through GFE plots, might be useful in predicting the stability and PZA-resistance behind mutation. This study provides useful information for better management of drug resistance, to control the global TB problem.

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Investigation of structural stability and functionality of homodimeric gramicidin towards peptide‐based drug: a molecular simulation approach

Cited by 12 publications

References 64 publications

Engineering a High-Affinity PD-1 Peptide for Optimized Immune Cell-Mediated Tumor Therapy

Engineering a High-Affinity PD-1 Peptide for Optimized Immune Cell-Mediated Tumor Therapy

An Overview of Molecular Dynamic Simulation for Corrosion Inhibition of Ferrous Metals

Gibbs Free Energy Calculation of Mutation in PncA and RpsA Associated With Pyrazinamide Resistance

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