RESEARCH: COVID-19
FOLDING PROJECT #17346 PROFILE

This project uses computer simulations to study how the SARS-CoV-2 virus attaches to human cells. They're looking at how sugar molecules on the virus affect its shape and how it binds to the ACE2 receptor. This information can help scientists design new 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) 17336-40 replace 17330, 32-35 (fix glycan stereoisomer) 17341-3 are repeats of 17336, 17337, and 17339 (RUN8), where each project has 5 RUNs starting from different equilibrated structures.

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SARS-CoV-2

Severe acute respiratory syndrome coronavirus 2

SARS-CoV-2 is the virus responsible for causing COVID-19. It's a type of coronavirus that spreads through respiratory droplets and can lead to severe respiratory illness.

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Receptor binding domain (RBD)

Receptor binding domain

The receptor binding domain (RBD) is a specific part of the SARS-CoV-2 spike protein. It's responsible for attaching to the ACE2 receptor on human cells, allowing the virus to infect them.

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ACE2

Angiotensin-converting enzyme 2

ACE2 is a protein found on the surface of many human cells. The SARS-CoV-2 virus uses its RBD to bind to ACE2, allowing it to enter and infect the cell.

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Glycosylation

The addition of sugar molecules to proteins

Glycosylation is a process where sugar molecules (glycans) are attached to proteins. This can change the protein's structure, function, and stability. In the case of SARS-CoV-2, glycosylation on the spike protein can affect its ability to bind to ACE2.

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Markov State Models

Mathematical models that describe the transitions between different states of a system

Markov State Models are used in computational simulations to understand how complex systems, like proteins, change over time. They can help predict the most likely states a protein will be in and how it might transition between them.

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Metastable States

States that a system can remain in for a long time but eventually transition to other states

Metastable states are like temporary resting points in a system's journey. A protein might spend a lot of time in a metastable state before changing into a different shape. Understanding these states can help us understand how proteins function and interact.

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Drug Design

The process of designing and developing new medications

Drug design involves using knowledge about diseases and biological processes to create new molecules that can treat or prevent them. This often includes understanding how a drug interacts with its target (like a protein) and how it affects the body.