Date of Award

2021-05-01

Degree Name

Master of Science

Department

Computational Science

Advisor(s)

Lin Li

Abstract

The ongoing outbreak of COVID-19 has been a serious threat to human health worldwide. The virus SARS-CoV-2 initiates its infection to the human body via the interaction of its spike (S) protein with the human Angiotensin-Converting Enzyme 2 (ACE2) of the host cells. Here we implemented multi-scale computational approaches to study the binding mechanisms of human ACE2 and S proteins of both SARS-CoV and SARS-CoV-2. Electrostatic features, including electrostatic potential, electric field lines and electrostatic forces of SARS-CoV and SARS-CoV-2 were calculated and compared in detail. The results demonstrate that SARS-CoV and SARS-CoV-2 S proteins are both attractive to ACE2 by electrostatic forces even at different distances. However, the residues contributing to the electrostatic features are quite different due to the mutations between SARS-CoV S protein and SARS-CoV-2 S protein. Compared to SARS-CoV, the SARS-CoV-2 binds with ACE2 using a more robust strategy: The electric field line related residues are distributed quite differently, which results in a more robust binding strategy of SARS-CoV-2. Also, SARS-CoV-2 has a higher electric field line density than that of SARS-CoV, which indicates stronger interaction between SARS-CoV-2 and ACE2, compared to that of SARS-CoV. Key residues involved in salt bridges and hydrogen bonds are identified in this study, which may help the future drug design against COVID-19.

Language

en

Provenance

Received from ProQuest

File Size

52 p.

File Format

application/pdf

Rights Holder

Yixin Xie

Included in

Biophysics Commons

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