RESEARCH: CANCER
FOLDING PROJECT #18228 PROFILE

This project uses computer simulations to study Phosphoglycerate kinase (PGK), a protein important for energy production in cells. The project aims to understand how PGK works at a structural level and how different simulation methods affect accuracy. Understanding PGK is important because it's linked to diseases like anemia and cancer, and can even affect how drugs work.

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

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

Phosphoglycerate kinase (PGK) is a vital enzyme involved in glycolysis, the process of breaking down sugar for energy. It catalyzes a key step in this process, converting one molecule into another while generating ATP, the cell's energy currency. PGK deficiencies can lead to health problems like anemia and muscle weakness, while its over-expression is linked to cancer development.

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Glycolysis

The metabolic pathway that converts glucose into pyruvate.

Glycolysis is a fundamental process in all living cells where glucose (sugar) is broken down to produce energy in the form of ATP. This ten-step pathway involves several enzymes and occurs in the cytoplasm of cells. It's essential for providing immediate energy for various cellular functions.

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ATP

Adenosine triphosphate

ATP stands for adenosine triphosphate. It's the primary energy currency of cells. When a phosphate group is removed from ATP (hydrolyzed), energy is released, powering various cellular processes like muscle contraction, nerve impulse transmission, and protein synthesis.

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Hemolytic anemia

A condition characterized by the destruction of red blood cells.

Hemolytic anemia occurs when red blood cells are destroyed faster than the bone marrow can replace them. This can lead to fatigue, weakness, pale skin, and shortness of breath. Various factors like genetic disorders, autoimmune diseases, or infections can cause hemolytic anemia.

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Myopathy

A disease or disorder of muscle tissue.

Myopathy refers to any condition affecting muscle function and structure. Symptoms can include muscle weakness, pain, fatigue, and difficulty with movement. Various causes like genetic disorders, infections, autoimmune diseases, or medications can lead to myopathy.

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Cancer

A group of diseases characterized by uncontrolled cell growth.

Cancer is a broad term encompassing various diseases marked by abnormal and rapid cell division. This uncontrolled growth can invade surrounding tissues and spread to other parts of the body (metastasis). Many factors like genetics, lifestyle, and environmental exposures contribute to cancer development.