RESEARCH: COVID-19
FOLDING PROJECT #17343 PROFILE

The project relates to studying how the SARS-CoV-2 virus attaches to human cells. Scientists are simulating the virus's binding part (RBD) and its target (ACE2) using computer models, with and without sugar molecules (glycosylation). This will help understand how glycosylation affects the virus's shape and how it binds to ACE2. The findings could aid in developing new drugs.

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.

SARS-CoV-2

Severe acute respiratory syndrome coronavirus 2

SARS-CoV-2 is a virus that causes COVID-19. It's a type of coronavirus, which are known for causing respiratory illnesses. Scientists study SARS-CoV-2 to understand how it spreads and to develop treatments and vaccines.

receptor binding domain (RBD)

Receptor Binding Domain

The RBD is a part of the SARS-CoV-2 virus's spike protein. This region binds to receptors on human cells, allowing the virus to enter and infect them.

ACE2

Angiotensin-converting enzyme 2

ACE2 is a protein found on the surface of human cells. The SARS-CoV-2 virus's RBD binds to ACE2, allowing it to enter and infect cells.

glycosylation

The process of adding sugar molecules to proteins

Glycosylation is a common way to modify proteins. It can change how a protein functions and interacts with other molecules. Scientists study glycosylation in viruses like SARS-CoV-2 to understand how it affects their ability to infect cells.

Markov State Models

Mathematical models used to simulate the behavior of molecules over time

Markov State Models are a tool used by scientists to study how molecules move and interact. They can be used to understand things like protein folding, drug binding, and viral infection.

metastable states

Temporary, stable configurations of molecules that are not the lowest energy state

Metastable states are like temporary resting points for molecules. They're not completely stable, but they last long enough to be important in biological processes. Scientists use Markov State Models to identify these metastable states and understand how molecules move between them.