RESEARCH: FORCE-FIELD-PROTEIN-DYNAMICS
FOLDING PROJECT #18237 PROFILE

This project tests different computer models used to simulate how proteins move. They use a well-studied protein called lysozyme to see which model is most accurate. The goal is to improve these simulations so scientists can better understand how proteins work.

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

Force fields aren't only a thing in far off galaxies, but are also an integral part of molecular dynamics simulations.

Principally, molecular dynamics simulations are evaluating Newton's laws of motion iteratively.

Each atom in the simulation is given a position, velocity, and has some forces acting upon it.

We then take a short step forward in time (often 2-4 femtoseconds), update the positions of each atom based on the last known position, velocity, and acceleration, before re-evaluating the forces acting upon each atom.

Repeating this millions to trillions of times (or more), gives us a physics-based movie of atoms moving which we use to give insight into the behavior of our favorite proteins. One of the fundamental steps of this process is calculating the forces on each atom.

The collective model describing how to calculate these forces is called a force field.

Through the years, many force fields have been derived and refined, each one focusing on improving certain forces or behaviors of the simulation.

While tests are usually performed when force fields are redeveloped, it is difficult to achieve robust sampling (e.g.

many observations of rare events).

Here, we are continuing our efforts to catalog the performance and accuracy of these force fields.

In this project series, we use the well studied protein, T4 Lysozyme, as our test model.

Lysozyme is an antibacterial protein which destroys bacterial cell walls.

Lysozyme is an ideal system to use for evaluating force fields as many biophysical measurements have been performed on the system and several rare conformations (folds) of the protein have been observed.

We expect that our findings in this project series, along with the similar project series 18227-18230 and 18250-18255, will provide a strong benchmark to improve the accuracy in simulations, both on Folding@home as well as in the broader scientific community, to come. We are testing the following force field/water combinations in this project series.

If you are particularly excited about additional force field/water combinations, please reach out. 18235- Amber03 with TIP3P water 18236- Amber14sb with TIP3P water 18237- Amber19sb with OPC water 18238- Charmm36m with TIP3P water 18239- Amber99SB-star-ILDN with TIP4PD water 18240- Amber99SB-disp with TIP4PD-1.6 water.

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Force fields

A collective model describing how to calculate the forces acting on atoms in a molecular dynamics simulation.

Force fields are mathematical models used in computer simulations to represent the interactions between atoms. They are essential for accurately simulating the behavior of molecules and understanding their properties.

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Molecular dynamics

A method for simulating the movement and interaction of atoms and molecules over time.

Molecular dynamics simulations use computer algorithms to model the behavior of molecules. By calculating the forces between atoms, these simulations can predict how molecules will move and interact, providing insights into chemical reactions, protein folding, and other biological processes.

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Newton's laws of motion

A set of three fundamental principles that govern the motion of objects.

Newton's laws of motion describe how objects move and interact with forces. These laws are essential for understanding the behavior of everything from planets to projectiles.

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Femtoseconds

A unit of time equal to 10^-15 seconds.

Femtoseconds are incredibly short units of time, used to measure the fastest events in physics and chemistry. They are often employed in studying ultrafast processes like light absorption and chemical reactions.

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T4 Lysozyme

A well-studied bacteriolytic enzyme.

T4 Lysozyme is a type of protein that breaks down bacterial cell walls. It is widely used as a model system in biochemistry and molecular biology research due to its simplicity and well-characterized structure.

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Folding@home

A distributed computing project that uses volunteer computer resources to perform simulations of protein folding.

Folding@home harnesses the power of thousands of computers to simulate the complex process of protein folding. This research helps scientists understand how proteins fold into their functional shapes and develop new drugs and therapies.