RESEARCH: FORCE-FIELD-PROTEIN-DYNAMICS
FOLDING PROJECT #18236 PROFILE

This project tests different computer models used to simulate how molecules move. They use a protein called T4 Lysozyme as a test subject because scientists already know a lot about it. The goal is to improve these models so they can better predict how proteins fold and behave.

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 computational model describing atomic interactions in a 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 are widely used in drug discovery, materials science, and other fields.

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Molecular dynamics

A computer simulation method used to study the movement and interactions of atoms and molecules over time.

Molecular dynamics simulations are a powerful tool for understanding how molecules behave. By simulating the motion of atoms and molecules, scientists can gain insights into processes such as protein folding, drug binding, and chemical reactions.

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Newton's laws of motion

A set of three fundamental principles describing the relationship between a body and the forces acting upon it.

Newton's laws of motion are the foundation of classical mechanics. They explain how objects move in response to forces and describe concepts such as inertia, acceleration, and momentum.

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Femtoseconds

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

Femtoseconds are extremely short durations of time. They are often used to measure the incredibly fast processes that occur in atomic and molecular systems.

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Protein

A large biomolecule composed of chains of amino acids.

Proteins are essential macromolecules that perform a vast array of functions in living organisms. They act as enzymes, structural components, hormones, and transporters, among other roles.

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T4 Lysozyme

A bacteriolytic enzyme that breaks down bacterial cell walls.

T4 lysozyme is a well-studied enzyme that has important applications in medicine and research. It is used to combat bacterial infections and as a model system for studying protein structure and function.

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Antibacterial

Relating to the inhibition or destruction of bacteria.

Antibacterial refers to substances or treatments that are effective against bacteria. These include antibiotics and other antimicrobial agents.

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Conformations

Different three-dimensional shapes that a molecule can adopt.

Conformations are the various spatial arrangements of atoms within a molecule. They play a crucial role in protein function and stability.