Speaker
Description
Molecular dynamics (MD) simulation is a powerful tool for understanding the structural and functional consequences of oxidative modifications in proteins, particularly cysteine oxidation. By providing atomic-level insights into how oxidative stress alters protein stability, dynamics, and interactions, MD simulations help elucidate the molecular mechanisms underlying disease progression. This approach is especially valuable in studying the effects of cysteine oxidation on proteins involved in cancer cell growth, viral infection, and membrane stability, offering potential implications for targeted therapeutic strategies.
One of the important amino acid residues that can play an essential role in the stability of protein structures is cysteine which can easily make disulfide bridges with other thiol groups and H-bonds with other amino acids. Moreover, cysteine is highly reactive and can be easily oxidized to cysteic acid by reactive oxygen species (ROS) generated inside the body or applied by cold atmospheric plasma. In general, intracellular ROS, such as H2O2, can oxidize 5% of Cys residues of proteins to cysteic or sulfunic acid [1], and this effect is enhanced under oxidative stress [2]. Plasma oxidation of amino acids in proteins, especially oxidation of the thiol groups of Cys residues, can disturb the normal function of some antioxidant enzymes [3]. Indeed, the ROS-induced protein modifications can alter the protein structure and disrupt their function [4]. In this presentation, we will describe the effect of Cys oxidation to cysteic acid on protein functions that are important in cancer cells growth and viral infection, using molecular dynamics simulations. Additionally, the importance of Cys residues in the stability of membrane proteins will be discussed.
[1] B.J. Williams, C.K. Barlow, K.L. Kmiec, W.K. Russell, D.H. Russell, Negative ion fragmentation of cysteic acid containing peptides: cysteic acid as a fixed negative charge, Journal of The American Society for Mass Spectrometry 22(9) (2011) 1622-1630.
[2] E. Takai, T. Kitamura, J. Kuwabara, S. Ikawa, S. Yoshizawa, K. Shiraki, H. Kawasaki, R. Arakawa, K. Kitano, Chemical modification of amino acids by atmospheric-pressure cold plasma in aqueous solution, Journal of Physics D: Applied Physics 47(28) (2014) 285403.
[3] D. Yan, A. Talbot, N. Nourmohammadi, X. Cheng, J. Canady, J. Sherman, M. Keidar, Principles of using cold atmospheric plasma stimulated media for cancer treatment, Scientific reports 5(1) (2015) 1-17.
[4] E. Cabiscol, J. Ros, Oxidative damage to proteins: structural modifications and consequences in cell function, Redox proteomics: from protein modification to cellular dysfunction and disease (2006) 399-471.
