RESEARCH: FORCE-FIELD-PROTEIN-SIMULATION
FOLDING PROJECT #18242 PROFILE

This project studies how well different computer models (force fields) simulate how proteins move and change shape. They're using a well-studied protein called lysozyme as a test case because lots of information is already known about it. The goal is to create better force fields that can accurately predict how proteins behave, which will help scientists understand diseases and design new drugs.

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 18240- Amber99SB-disp with TIP4PD-1.6 water 18242-Amber99SB-star-ILDN with TIP4PD water 18243- Amber19sb with OPC3 water 18244-Amber19sb with OPC3-pol water.

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Force fields

Mathematical models describing interactions between atoms in molecular simulations.

Force fields are used in computer simulations to represent the forces acting between atoms. They allow scientists to study how molecules move and interact, providing insights into biological processes and material properties.

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Molecular dynamics

Simulation of molecular motion based on Newton's laws of physics.

Molecular dynamics simulations are used to study the movement and interactions of atoms and molecules over time. This helps researchers understand how proteins fold, how drugs bind to targets, and other complex biological processes.

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Newton's laws of motion

Fundamental principles describing the relationship between force, mass, and motion.

Newton's laws of motion are essential for understanding how objects move. They describe how a force applied to an object changes its velocity, and how objects interact with each other through forces.

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Atom

The basic building block of matter.

Atoms are the smallest units of an element that retain its chemical properties. They consist of a nucleus containing protons and neutrons, surrounded by electrons.

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Protein

Large biomolecules essential for various biological functions.

Proteins are complex molecules made up of amino acids. They perform a wide range of functions in living organisms, including catalyzing reactions, transporting molecules, and providing structural support.

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Lysozyme

An enzyme that breaks down bacterial cell walls.

Lysozyme is a protein found in tears, saliva, and mucus that helps defend against bacterial infections. It works by breaking down the peptidoglycan layer in bacterial cell walls.