RESEARCH: COVID-19
FOLDING PROJECT #17325 PROFILE

This project looks at how the SARS-CoV-2 spike protein interacts with human cells. They're using computer simulations to see how these proteins move and change shape, especially when they're connected. This can help us 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.

---

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. Understanding its structure and how it interacts with human cells is crucial for developing treatments and vaccines.

---

receptor binding domain (RBD)

Receptor Binding Domain

The RBD is a specific part of the SARS-CoV-2 spike protein that attaches to the ACE2 receptor on human cells. This binding is essential for the virus to enter and infect cells.

---

ACE2

Angiotensin-converting enzyme 2

ACE2 is a protein found on the surface of many human cells. It's involved in regulating blood pressure and other bodily functions. The SARS-CoV-2 virus uses ACE2 as its entry point into human cells.

---

glycosylation

The process of attaching sugar molecules to proteins

Glycosylation is a common way that cells modify proteins. It can affect how proteins fold, interact with other molecules, and function. In the case of SARS-CoV-2, glycosylation of the RBD may influence how it binds to ACE2.

---

Markov State Models

Mathematical models used to simulate the dynamics of complex systems

Markov State Models are a powerful tool for studying how molecules move and change over time. They can be used to understand the behavior of proteins like RBD and ACE2, and to predict how drugs might interact with them.

---

metastable states

Temporary, stable configurations of a molecule

Proteins can exist in different states. Metastable states are like temporary resting points on the path between these states. Understanding how proteins shift between metastable states is important for understanding their function and how drugs might affect them.

---

drug design

The process of developing new drugs

Drug design involves identifying promising molecules that can interact with specific targets in the body (like proteins) to treat diseases. Understanding how RBD and ACE2 interact can help researchers design drugs that block this interaction and prevent viral infection.