RESEARCH: COVID-19
FOLDING PROJECT #17321 PROFILE

This project studies how the SARS-CoV-2 spike protein binds to human cells. They're using computer simulations to see how the proteins change shape and how sugar molecules affect these changes. This helps scientists understand how the virus works and design better drugs to fight it.

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.

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SARS-CoV-2

Severe acute respiratory syndrome coronavirus 2

SARS-CoV-2 is a virus responsible for causing COVID-19. It's a type of coronavirus that can infect the respiratory system, leading to symptoms like fever, cough, and difficulty breathing.

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receptor binding domain (RBD)

Region of a protein that binds to a receptor

The RBD is a part of the SARS-CoV-2 spike protein responsible for attaching to human cells. It interacts with the ACE2 receptor on cell surfaces, allowing the virus to enter and infect.

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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, enabling it to enter and infect those cells.

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glycosylation

The process of attaching sugar molecules to proteins

Glycosylation is a common modification that occurs on many proteins. It can affect protein structure, function, and stability. In the case of SARS-CoV-2, glycosylation patterns on the spike protein may influence its ability to bind to ACE2.

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Markov State Models

Mathematical models used to describe the behavior of complex systems over time

Markov State Models are used to simulate and analyze the movement of molecules. In this case, they will be applied to study the conformational dynamics of SARS-CoV-2 proteins and their complexes.

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metastable states

States that a molecule can occupy for extended periods but are not the lowest energy state

Proteins exist in different shapes or conformations. Metastable states are temporary shapes that a protein can hold before transitioning to other more stable forms. Understanding these states can provide insights into protein function and dynamics.

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drug design

The process of developing new drugs

Drug design involves identifying and optimizing molecules that can target specific biological processes to treat diseases. Understanding the mechanisms of viral infection and protein interactions is crucial for designing effective antiviral drugs.