Molecular dynamics simulations of spike protein interaction with viral membrane

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Perustieteiden korkeakoulu | Bachelor's thesis
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Date

2024-10-11

Department

Major/Subject

Teknillinen fysiikka

Mcode

SCI3028

Degree programme

Teknistieteellinen kandidaattiohjelma

Language

en

Pages

38

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Abstract

Molecular dynamics (MD) is a computational technique used to study the properties and predict the motion of classical molecular systems. MD simulations have various applications in biophysics, bioinformatics and chemistry, including drug design, protein allostery research, and structure prediction. MD simulations are based on calculating the forces acting on each atom, which allows for determining the time evolution of the system. SARS-CoV-2, the causal agent of the coronavirus disease 2019 (COVID-19), caused a global pandemic in 2020. SARS-CoV-2 consists of four structural proteins, from which the spike (S) protein is considered to be the most crucial. At the cellular level, the S protein binds to the ACE2 receptor and enables the virus’s entry into the host cell. It undergoes a process of S-palmitoylation, where a palmitic acid attaches to a cysteine residue. Previous research has indicated that palmitoylation increases protein hydrophobicity and contributes significantly to protein stability, trafficking, and interaction with other proteins. In this thesis, we studied the spike protein of SARS-CoV-2 in viral membrane using MD simulations. In addition, we investigated whether cysteine palmitoylation affects the stability of the spike protein in the viral membrane. This was examined by performing constant-velocity steered MD (SMD) simulations, where we pulled the tail of the spike protein out of the membrane. Furthermore, we evaluated the stability of the spike protein by calculating free energy profiles using the Jarzynski equality. We also determined the appropriate parameters for the SMD simulations. Root mean square deviation (RMSD) values calculated in this work showed that the protein achieved a stable structure during the production of particle dynamics. However, the results obtained from the SMD simulations were partly contrary to the previous research, which showed that palmitoylation should increase protein stability. These conflicting results are most likely due to choosing unsuitable parameter values for applying the Jarzynski equality. In addition, more samples of the SMD simulations should be collected to obtain more reliable results.

Description

Supervisor

Ala-Nissilä, Tapio

Thesis advisor

Ghasemitarei, Maryam

Keywords

molecular dynamics simulation, spike protein, SARS-CoV-2, viral membrane, palmitoylation

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https://urn.fi/URN:NBN:fi:aalto-202410226815

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[kand] Perustieteiden korkeakoulu / SCI