RESEARCH: FORCE-FIELD-PROTEIN
FOLDING PROJECT #18239 PROFILE

This project uses computer simulations to study how proteins move and fold. They're testing different 'force fields', which are like rules for how atoms interact, using a well-studied protein called T4 lysozyme. The goal is to improve the accuracy of these simulations, helping scientists 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- 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

Mathematical models used to describe interactions between atoms in molecular simulations.

Force fields are like rulesets that govern how atoms interact with each other in computer simulations. They're essential for accurately predicting the movement and behavior of molecules, which is crucial for understanding biological processes.

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molecular dynamics

Computer simulations that model the movement of atoms and molecules over time.

Molecular dynamics simulations are like virtual laboratories where scientists can observe how atoms and molecules interact. By running these simulations, researchers can gain insights into biological processes at the atomic level.

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Newton's laws of motion

Fundamental principles that describe the relationship between force, mass, and motion.

Newton's laws of motion are the bedrock of classical mechanics. They explain how objects move and interact based on forces applied to them. These laws are essential for understanding everything from the trajectory of a ball to the movement of planets.

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femtoseconds

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

Femtoseconds are incredibly short bursts of time. They're used to measure the extremely fast movements of atoms and molecules.

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T4 Lysozyme

An enzyme that breaks down bacterial cell walls.

T4 Lysozyme is a powerful protein that helps protect us from bacteria. It works by breaking down the cell walls of bacteria, effectively killing them.

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conformations

Different three-dimensional shapes that a protein can adopt.

Proteins are like tiny machines with many moving parts. Their shape is crucial for their function. Conformations refer to the different ways a protein can fold and rearrange itself.

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Folding@home

A distributed computing project that simulates protein folding.

Folding@home harnesses the power of thousands of computers to simulate how proteins fold. This helps researchers understand diseases and develop new drugs.