RESEARCH: FORCE-FIELD-ACCURACY
FOLDING PROJECT #18241 PROFILE

This project tests different computer models used to simulate how proteins move and fold. They use a protein called T4 Lysozyme, which is good for testing because scientists already know a lot about it. The goal is to create more accurate simulations that can help us 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- Amber19sb with OPC3 water 18240- Amber99SB-disp with TIP4PD-1.6 water 18241-Amber19sb with OPC3-pol water 18242-Amber99SB-star-ILDN with TIP4PD water.

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Force fields

A model describing how forces act on atoms in a simulation.

Force fields are mathematical models used in computer simulations to describe the interactions between atoms. They are crucial for accurately simulating the behavior of molecules, such as proteins.

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Molecular dynamics

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

Molecular dynamics simulations use Newton's laws of motion to track the movement of atoms in a system. These simulations are used to understand how molecules interact and behave.

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Newton's laws of motion

Fundamental principles governing the motion of objects.

Newton's laws of motion describe how objects move and interact. These laws are essential for understanding motion in everyday life and in scientific fields.

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Femtoseconds

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

Femtoseconds are extremely short units of time used to measure events that happen very quickly, such as the movement of atoms.

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Proteins

Large, complex molecules essential for various biological functions.

Proteins are the workhorses of cells, carrying out a vast array of tasks, from catalyzing reactions to transporting molecules.

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Lysozyme

An enzyme that breaks down bacterial cell walls.

Lysozyme is an important part of the immune system. It helps to protect us from bacterial infections by destroying their cell walls.