RESEARCH: FORCE-FIELD-PROTEIN-DYNAMICS
FOLDING PROJECT #18238 PROFILE

The project uses computer simulations to study how proteins move and fold. Scientists are testing different simulation methods (called force fields) by looking at a protein called T4 Lysozyme, which helps fight bacteria. This research will help improve simulations and our understanding of 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 computational model used in molecular dynamics simulations to describe the interactions between atoms.

Force fields are mathematical models that define how atoms interact with each other. They are essential for molecular dynamics simulations, which are used to study the movement and behavior of molecules.

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Molecular Dynamics

A computational method used to simulate the movement and behavior of atoms and molecules over time.

Molecular Dynamics (MD) simulations use computer algorithms to mimic the physical interactions between atoms in a system. This allows researchers to study how molecules move, interact, and change shape over time.

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Newton's laws of motion

A set of three fundamental laws that describe the relationship between a body and the forces acting upon it, and its motion in response to those forces.

Newton's Laws of Motion are foundational principles in physics. They explain how objects move and interact with forces. The first law describes inertia, the second law relates force, mass, and acceleration, and the third law states that for every action, there is an equal and opposite reaction.

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Femtoseconds

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

Femtoseconds are incredibly short units of time, used to measure extremely fast events at the atomic and subatomic level. One femtosecond is one quadrillionth of a second.

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Protein

A large biomolecule made up of chains of amino acids.

Proteins are essential macromolecules found in all living organisms. They perform a wide range of functions, including catalyzing biochemical reactions, transporting molecules, providing structural support, and regulating cellular processes.

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Lysozyme

An enzyme that breaks down bacterial cell walls.

Lysozyme is an antimicrobial enzyme found in tears, saliva, and mucus. It acts by breaking down the peptidoglycan layer of bacterial cell walls, leading to bacterial lysis (cell death).

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Conformations

The different three-dimensional shapes that a protein can adopt.

Proteins are not rigid structures but can fold into various shapes called conformations. These different conformations allow proteins to perform their diverse functions.

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Folding@home

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

Folding@home is a massive scientific effort that harnesses the power of many computers to simulate the complex process of protein folding. Volunteers donate their computer's processing power to help researchers understand how proteins fold and function.