The effect of cysteine oxidation on conformational changes of SARS-CoV-2 spike protein using atomistic simulations.

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Tác giả: Tapio Ala-Nissila, Annemie Bogaerts, Maryam Ghasemitarei, Tayebeh Ghorbi, Hoda Taeb, Maksudbek Yusupov

Ngôn ngữ: eng

Ký hiệu phân loại: 363.737 Measures to prevent, protect against, limit effects of pollution

Thông tin xuất bản: England : Scientific reports , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 681271

The SARS-CoV-2 Spike (S) protein plays a central role in viral entry into host cells, making it a key target for therapeutic interventions. Oxidative stress, often triggered during viral infections, can cause oxidation of cysteine in this protein. Here we investigate the impact of cysteine oxidation, specifically the formation of cysteic acid, on the conformational dynamics of the SARS-CoV-2 S protein using atomistic simulations. In particular, we examine how cysteine oxidation influences the transitions of the S protein's receptor-binding domain (RBD) between "down" (inaccessible) and "up" (accessible) states, which are critical for host cell receptor engagement. Using solvent-accessible surface area (SASA) analysis, we identify key cysteine residues susceptible to oxidation. The results of targeted molecular dynamics (TMD) and umbrella sampling (US) simulations reveal that oxidation reduces the energy barrier for RBD transitions by approximately 30 kJ mol
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