RESEARCH: COVID-19
FOLDING PROJECT #17340 PROFILE

This project uses computer simulations to study how the SARS-CoV-2 spike protein binds to human cells. By looking at different versions of the proteins with and without sugars, researchers hope to understand how these sugars affect the binding process and potentially identify new drug targets.

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).

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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 easily between people through respiratory droplets. Symptoms can range from mild to severe, including fever, cough, shortness of breath, and fatigue.

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RBD

Receptor Binding Domain

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

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Glycosylation

The process of adding sugar molecules to proteins.

Glycosylation is a common modification of proteins that can affect their function. In the context of SARS-CoV-2, glycosylation of the RBD can influence its binding to the ACE2 receptor.

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Markov State Models

Mathematical models used to simulate the dynamic behavior of complex systems.

Markov state models are used to study the different states that a protein can exist in and how it transitions between them. This can help us understand how proteins function and how they are affected by changes in their environment.

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Metastable States

States that a system can remain in for a relatively long time but are not truly stable.

Metastable states are important because they represent intermediate stages in the process of protein folding and other biological reactions. Understanding these states can help us design more effective drugs and therapies.

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Drug Design

The process of discovering and developing new medications.

Drug design is a complex process that involves identifying potential drug targets, designing molecules that can bind to these targets, and testing the efficacy and safety of the resulting drugs.