RESEARCH: CANCER
FOLDING PROJECT #18227 PROFILE

This project uses computer simulations to study how the protein Phosphoglycerate kinase (PGK) works. PGK is important for energy production in cells and problems with it can cause health issues. By simulating PGK, researchers hope to understand its structure and function better. They are also testing different simulation methods to see which ones are most accurate.

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 understoon, 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 and 18228, we look at how the force fields amber03 and amber14sb perform.

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

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Phosphoglycerate kinase

Enzyme catalyzing a key step in glycolysis.

Phosphoglycerate kinase (PGK) is an enzyme essential for cellular energy production. It plays a crucial role in glycolysis, the process of breaking down sugar to generate ATP (the cell's energy currency). PGK catalyzes a specific reaction converting 1,3-bisphosphoglycerate to 3-phosphoglycerate, releasing energy used to form ATP.

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Glycolysis

Metabolic pathway converting glucose to pyruvate.

Glycolysis is a fundamental metabolic pathway that breaks down glucose into pyruvate. This process occurs in the cytoplasm of cells and is essential for energy production. During glycolysis, glucose is sequentially converted through several enzymatic reactions, ultimately generating ATP (the cell's energy currency) and pyruvate.

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ATP

Adenosine triphosphate

ATP (Adenosine Triphosphate) is the primary energy currency of cells. It stores and releases energy in a readily usable form for cellular processes such as muscle contraction, protein synthesis, and nerve impulse transmission.

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Hemolytic anemia

Anemia caused by red blood cell destruction.

Hemolytic anemia is a type of anemia characterized by the premature destruction of red blood cells. This can lead to fatigue, weakness, pale skin, and shortness of breath. Causes include genetic disorders, autoimmune diseases, infections, and certain medications.

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Myopathy

Disease affecting muscle function.

Myopathy is a general term for any disease that affects muscle function. This can lead to weakness, pain, stiffness, and difficulty moving. Causes include genetic disorders, infections, autoimmune diseases, and certain medications.

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Cancer

Uncontrolled cell growth.

Cancer is a group of diseases characterized by uncontrolled cell growth and spread. This can damage surrounding tissues and organs. Causes include genetic mutations, environmental factors, and lifestyle choices.

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Force field

Model of molecular interactions.

A force field is a mathematical model used in computer simulations to represent the interactions between atoms and molecules. It describes how atoms attract and repel each other based on their distance and electronic properties. Force fields are essential for simulating the behavior of complex biological systems.