Effects of Nitro-Oxidative Stress on Biomolecules: Part 1—Non-Reactive Molecular Dynamics Simulations

Abstract

Plasma medicine, or the biomedical application of cold atmospheric plasma (CAP), is an expanding field within plasma research. CAP has demonstrated remarkable versatility in diverse biological applications, including cancer treatment, wound healing, microorganism inactivation, and skin disease therapy. However, the precise mechanisms underlying the effects of CAP remain incompletely understood. The therapeutic effects of CAP are largely attributed to the generation of reactive oxygen and nitrogen species (RONS), which play a crucial role in the biological responses induced by CAP. Specifically, RONS produced during CAP treatment have the ability to chemically modify cell membranes and membrane proteins, causing nitro-oxidative stress, thereby leading to changes in membrane permeability and disruption of cellular processes. To gain atomic-level insights into these interactions, non-reactive molecular dynamics (MD) simulations have emerged as a valuable tool. These simulations facilitate the examination of larger-scale system dynamics, including protein-protein and protein-membrane interactions. In this comprehensive review, we focus on the applications of non-reactive MD simulations in studying the effects of CAP on cellular components and interactions at the atomic level, providing a detailed overview of the potential of CAP in medicine. We also review the results of other MD studies that are not related to plasma medicine but explore the effects of nitro-oxidative stress on cellular components and are therefore important for a broader understanding of the underlying processes.

Unraveling the influence of nitration on pore formation time in electroporation of cell membranes: a molecular dynamics simulation approach

“…Notably, nitro groups, due to their electronic delocalization, act as superior water transporters into the membrane interior compared to ketone groups [68]. This observation aligns with the notion that nitrooxidation products with highly charged groups elevate membrane permeability [32]. The study concludes by emphasizing the increased susceptibility of membranes with nitrated lipids to pore formation, crucial for understanding the implications of nitro-oxidative stress in various cancer therapies [69].…”

“…The primary objective of this study is to investigate the influence of nitration on the pore formation time during electroporation, employing MD simulations [31,32]. To achieve this goal, the study will first establish a suitable MD simulation setup and define the parameters necessary for accurately modeling the electroporation process in the presence of nitrated molecules [33,34].…”

Bacterial Decontamination of Water-Containing Objects Using Piezoelectric Direct Discharge Plasma and Plasma Jet

“…Furthermore, CAP has been found to modulate cellular processes. It can influence cell signaling pathways, leading to alterations in gene expression and cell behavior [26,27]. This capability led to therapeutic applications, such as in wound healing and cancer treatment [28][29][30].…”

Modeling Study of OH Radical-Dominated H-Abstraction Reaction for Understanding Nucleotides Oxidation Induced by Cold Atmospheric Plasmas

“…ROS have been shown to interact with various macromolecules, exerting profound effects on cells, including the oxidation of cell membranes, proteins, and DNA during the sterilization process of CAP [15][16][17]. Furthermore, ROS function as pivotal intracellular signal regulators, modulating numerous cellular signaling pathways through diverse mechanisms instrumental in cell transformation, inflammatory responses, tumor proliferation, and metastasis [18,19]. However, it remains elusive the exact interaction mechanism among reactive species and biomolecules.…”