Structural stability of antimicrobial peptides rich in tryptophan, proline and arginine: a computational study

Marimuthu, Sathish Kumar; Nagarajan, Krishnanand; Perumal, Sathish Kumar; Palanisamy, Selvamani; Latha, S.

doi:10.1080/07391102.2020.1848631

Cited by 6 publications

(3 citation statements)

References 41 publications

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“…In this simulation, residues 18–29 were observed to be the crucial region of LL-37, as they actively interact with the POPE:POPG membrane while retaining its helical properties. These are also in agreement with the previous study of LL-37 as a helix rich in positively charged side chains, allowing efficient interaction with anionic phosphatidylglycerols in bacterial membranes [ 34 , 35 ]. For some other AMPs, helical formation is also an important structural element that possesses antimicrobial capability [ 22 ].…”

Section: Discussionsupporting

confidence: 93%

Residual Interactions of LL-37 with POPC and POPE:POPG Bilayer Model Studied by All-Atom Molecular Dynamics Simulation

Yusuf

Destiarani

Firdaus

et al. 2022

IJMS

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LL-37 is a membrane-active antimicrobial peptide (AMP) that could disrupt the integrity of bacterial membranes due to its inherent cationic and amphipathic nature. Developing a shorter derivative of a long peptide such as LL-37 is of great interest, as it can reduce production costs and cytotoxicity. However, more detailed information about the residual interaction between LL-37 and the membrane is required for further optimization. Previously, molecular dynamics simulation using mixed all-atom and united-atom force fields showed that LL-37 could penetrate the bilayer membrane. This study aimed to perform all-atom molecular dynamics simulations, highlighting the residual interaction of LL-37 with the simplest model of the bacterial membrane, POPE:POPG (2:1), and compare its interaction with the POPC, which represents the eukaryotic membrane. The result showed leucine–leucine as the leading residues of LL-37 that first contact the membrane surface. Then, the cationic peptide of LL-37 started to penetrate the membrane by developing salt bridges between positively charged amino acids, Lys–Arg, and the exposed phosphate group of POPE:POPG, which is shielded in POPC. Residues 18 to 29 are suggested as the core region of LL-37, as they actively interact with the POPE:POPG membrane, not POPC. These results could provide a basis for modifying the amino acid sequence of LL-37 and developing a more efficient design for LL-37 derivatives.

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Section: Discussionsupporting

confidence: 93%

Residual Interactions of LL-37 with POPC and POPE:POPG Bilayer Model Studied by All-Atom Molecular Dynamics Simulation

Yusuf

Destiarani

Firdaus

et al. 2022

IJMS

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“…To this purpose, two major groups can be distinguished: linear and cyclic peptides. Linear peptides encompass (1) linear peptides with α‐helical structures and no cysteines in their sequences; (2) linear peptides with predominantly β‐sheet structures containing multiple disulfide bonds (Andreu & Rivas, 1998 ); (3) random coiled peptides rich in proline, arginine, tryptophan and/or histidine (Marimuthu et al, 2020 ). A large number of X‐ray and 2D‐NMR experiments (both in solution and in membrane mimetics) were reported to identify and determine the secondary and tertiary structures of such linear peptides (Ramamoorthy, 2009 ; Zhang et al, 1992 ).…”

Section: Molecular Structure‐based Classification Of Antibacterialsmentioning

confidence: 99%

Structure–activity relationships of antibacterial peptides

Ciulla

Gelain

2023

Microbial Biotechnology

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Antimicrobial peptides play a crucial role in innate immunity, whose components are mainly peptide‐based molecules with antibacterial properties. Indeed, the exploration of the immune system over the past 40 years has revealed a number of natural peptides playing a pivotal role in the defence mechanisms of vertebrates and invertebrates, including amphibians, insects, and mammalians. This review provides a discussion regarding the antibacterial mechanisms of peptide‐based agents and their structure–activity relationships (SARs) with the aim of describing a topic that is not yet fully explored. Some growing evidence suggests that innate immunity should be strongly considered for the development of novel antibiotic peptide‐based libraries. Also, due to the constantly rising concern of antibiotic resistance, the development of new antibiotic drugs is becoming a priority of global importance. Hence, the study and the understanding of defence phenomena occurring in the immune system may inspire the development of novel antibiotic compound libraries and set the stage to overcome drug‐resistant pathogens. Here, we provide an overview of the importance of peptide‐based antibacterial sources, focusing on accurately selected molecular structures, their SARs including recently introduced modifications, their latest biotechnology applications, and their potential against multi‐drug resistant pathogens. Last, we provide cues to describe how antibacterial peptides show a better scope of action selectivity than several anti‐infective agents, which are characterized by non‐selective activities and non‐targeted actions toward pathogens.

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“…Previously, antimicrobial peptides with high tryptophan, proline, and arginine residues were collected and their three-dimensional structures evaluated. For this study, we used those three-dimensional peptide structures [14]. The crystal structure of the EGFR kinase domain protein was used as the target protein (PDB ID: 6ZJ0).…”

Section: Peptides and Protein Preparationmentioning

confidence: 99%

Interactions and stability of tryptophan, proline and arginine rich peptides with EGFR kinase and its anticancer activities – insilico approaches

Marimuthu

Nagarajan

Palanisamy

et al. 2022

Preprint

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Lung cancer is a major public health concern due to its high prevalence and mortality, and it is also the second leading cause of cancer death worldwide. Non-small cell lung cancer accounts for more than 80% of lung cancers. In recent years, the use of bioactive peptides in cancer therapy has widened the treatment regimen. They have been confirmed to selectively target and destroy cancer cells while leaving healthy cells unaffected. Furthermore, antimicrobial peptides can cause cytotoxic activity in human cancer cells by binding to negatively charged phosphatidylserine moieties on the outer surface of cancer cell plasma membranes. In the present study, we predicted the interactions of tryptophan, proline, and arginine-rich peptides with EGFR kinase and evaluated the protein-peptide complex stability through molecular dynamics simulations. From the computational study, we selected the potential peptides based on the docking score, the number of hydrogen bonds formed between the protein-peptide complexes and the stability. These results suggest that antimicrobial peptides show potential for application in lung cancer therapies.

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Structural stability of antimicrobial peptides rich in tryptophan, proline and arginine: a computational study

Cited by 6 publications

References 41 publications

Residual Interactions of LL-37 with POPC and POPE:POPG Bilayer Model Studied by All-Atom Molecular Dynamics Simulation

Residual Interactions of LL-37 with POPC and POPE:POPG Bilayer Model Studied by All-Atom Molecular Dynamics Simulation

Structure–activity relationships of antibacterial peptides

Interactions and stability of tryptophan, proline and arginine rich peptides with EGFR kinase and its anticancer activities – insilico approaches

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