RESEARCH: COVID-19
FOLDING PROJECT #17330 PROFILE

This project studies how the SARS-CoV-2 virus attaches to human cells. Researchers are using computer simulations to understand how the virus's protein (RBD) changes shape when it binds to a receptor on our cells (ACE2). They're also looking at how sugar molecules attached to these proteins affect their shape and binding. This knowledge will help scientists design better drugs to fight COVID-19.

Note: This TLDR is a simplication and may not be 100% accurate.

These projects involve the SARS-CoV-2 receptor binding domain (RBD) and its target receptor in humans, ACE2.

We are simulating these proteins alone and in complex with each other (and with and without glycosylation).

We will build Markov State Models using the Fah simulation data, which will help us identify the metastable states of each protein/protein complex.

Given these experiments, we hope to be able to explain the impact of glycosylation on RBD conformational dynamics as well as identify whether there are shifts in metastable states upon RBD:ACE2 binding.

Ultimately, the knowledge gained here will help infom drug design efforts. Note: 17313-6 replace 17307-9, as 17307-9 used a different, less stable integrator. 17329-331 replace 17316-8 (change from rectangular to truncated octahedron box) 17332-5 replace 17325-8 ((change from rectangular to truncated octahedron box).

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SARS-CoV-2

Severe acute respiratory syndrome coronavirus 2

SARS-CoV-2 is the virus that causes COVID-19. It is a type of coronavirus that primarily affects the respiratory system. Understanding its structure and how it interacts with human cells is crucial for developing treatments and vaccines.

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receptor binding domain (RBD)

Receptor Binding Domain

The RBD is a specific region on the surface of SARS-CoV-2 that binds to the ACE2 receptor on human cells, allowing the virus to enter and infect them. This interaction is essential for viral replication.

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ACE2

Angiotensin-converting enzyme 2

ACE2 is a protein found on the surface of many human cells, including those in the lungs and heart. It plays a role in regulating blood pressure and fluid balance. SARS-CoV-2 uses ACE2 as its entry point into human cells.

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glycosylation

The process of adding sugar molecules to proteins.

Glycosylation is a crucial process that modifies proteins and influences their function, stability, and interactions. In the context of SARS-CoV-2, glycosylation can affect how the virus binds to human cells and evade the immune system.

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Markov State Models

Mathematical models used to simulate the behavior of complex systems over time.

Markov State Models are powerful tools for understanding protein dynamics and identifying stable states. By simulating the movements of atoms in proteins, researchers can gain insights into how they fold, interact with other molecules, and carry out their functions.

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metastable states

Transient states that are relatively stable but can eventually transition to other states.

Metastable states represent different conformations or configurations of a protein. Understanding these states is crucial for comprehending how proteins function and respond to changes in their environment.

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drug design

The process of identifying and developing new drugs to treat diseases.

Drug design involves a multidisciplinary approach that combines chemistry, biology, and computational modeling to create molecules with specific therapeutic effects. Understanding how viruses like SARS-CoV-2 interact with human cells is essential for designing effective antiviral drugs.