RESEARCH: CANCER
FOLDING PROJECT #18230 PROFILE

This project simulates the protein PGK, which is important for energy production in cells. Scientists want to understand how PGK works at a detailed level because it's involved in many diseases and drug metabolism. They are testing different computer simulation methods to see which one best matches real-world measurements of PGK.

Note: This TLDR is a simplication and may not be 100% accurate.

In this project we simulate the protein Phosphoglycerate kinase (PGK), a vital component in cell metabolism (specifically glycolysis, the processing of sugar into ATP for the cell).

PGK catalyzes the conversion of 1,3 bisphosphoglycerate to 3-phosphoglycerate generating one molecule of ATP in the process.

While the biochemical activity of PGK has been long understood, how this process is achieved from a structural perspective is less well known. PGK deficiencies lead to hemolytic anemia and myopathy, over-expression has been linked to a variety of cancers, and PGK can metabolize a variety of different drugs.

We hope that simulations of PGK will lead to a better understanding of how PGK completes these essential catalytic activities. In our prior projects we have looked at the impact of ligands on PGK conformations.

As our experimental collaborators have several biophysical measurements of PGK, we also believe this gives us an excellent opportunity to assess how force fields, one of the fundamental processes of our computer simulations, affect the accuracy of our simulations.

In project 18224, we looked at a commonly used force field, charmm36 performed.

In 18227-18230 we look at how the force fields amber03 (18227), amber14sb (18228), and amber19sb (18230) perform with their cognate water models.

We believe these findings will aid not only this project, but all simulation projects going forward.

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Phosphoglycerate kinase

An enzyme that catalyzes the conversion of 1,3-bisphosphoglycerate to 3-phosphoglycerate in glycolysis.

Phosphoglycerate kinase (PGK) is a crucial enzyme involved in cellular energy production. It plays a key role in glycolysis, the process where glucose is broken down to generate ATP, the cell's primary energy source. PGK catalyzes a specific step in this pathway, converting 1,3-bisphosphoglycerate to 3-phosphoglycerate, yielding one molecule of ATP.

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Glycolysis

The metabolic pathway that converts glucose into pyruvate, generating ATP.

Glycolysis is a fundamental biological process where glucose, a simple sugar, is broken down into pyruvate. This process occurs in the cytoplasm of cells and generates a small amount of ATP, the cell's primary energy currency. Glycolysis is an anaerobic pathway, meaning it does not require oxygen. It is the first step in cellular respiration, the overall process of extracting energy from glucose.

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ATP

Adenosine triphosphate

ATP stands for adenosine triphosphate. It is the primary energy currency of cells. ATP stores chemical energy in its phosphate bonds and releases this energy when these bonds are broken. Cells use ATP to power a wide range of processes, including muscle contraction, protein synthesis, and nerve impulse transmission.

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Hemolytic anemia

A condition in which red blood cells are destroyed faster than they can be produced.

Hemolytic anemia is a group of disorders characterized by the premature destruction of red blood cells. This leads to a decrease in the number of circulating red blood cells and can result in symptoms such as fatigue, weakness, shortness of breath, and jaundice. Causes of hemolytic anemia include genetic defects, autoimmune diseases, infections, and certain medications.

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Myopathy

A disease or disorder of the muscles.

Myopathy is a broad term that encompasses various conditions affecting muscle structure and function. Symptoms can range from muscle weakness and pain to difficulty with movement and coordination. Myopathies can be caused by genetic factors, autoimmune diseases, infections, nutritional deficiencies, and certain medications.

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Cancer

A group of diseases characterized by the uncontrolled growth and spread of cells.

Cancer is a complex group of diseases marked by abnormal cell growth and proliferation. These rogue cells can invade surrounding tissues and spread to other parts of the body (metastasis). Cancer arises from mutations in genes that control cell growth and division, leading to uncontrolled proliferation. There are many types of cancer, each with its own characteristics and treatments.