RESEARCH: FORCE-FIELD-PROTEIN-SIMULATION
FOLDING PROJECT #18243 PROFILE

The project relates to testing different computer models used to simulate how molecules move. These models are like physics rules for atoms and are important for understanding how proteins fold and work. Scientists are using a protein called lysozyme as a test case because it's well-studied and has many known shapes. This research aims to improve the accuracy of these simulations, which can help us learn more about diseases and develop 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

A model describing how to calculate forces on atoms in a simulation.

Force fields are mathematical models used in molecular dynamics simulations to calculate the forces acting between atoms. They are essential for accurately simulating the behavior of molecules and understanding their properties.

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Molecular dynamics

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

Molecular dynamics simulations are computer programs that use physical laws to simulate how atoms and molecules interact. This allows scientists to study the behavior of molecules in different environments and conditions.

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Newton's laws of motion

The fundamental principles governing the motion of objects.

Newton's laws of motion describe how objects move and interact with forces. They are the foundation of classical mechanics and are essential for understanding many phenomena in physics, including molecular dynamics.

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Femtoseconds

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

Femtoseconds are incredibly short units of time, often used in physics and chemistry to measure the speed of events at the atomic level. In molecular dynamics simulations, femtoseconds represent the small time steps taken to update the positions of atoms.

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Proteins

Large, complex molecules essential for many biological processes.

Proteins are the workhorses of cells, carrying out a vast array of functions. They are involved in everything from building and repairing tissues to catalyzing chemical reactions.

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T4 Lysozyme

A well-studied enzyme with antibacterial properties.

T4 Lysozyme is a protein that breaks down the cell walls of bacteria. It is used extensively in research to study protein structure and function.

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Conformations

Different shapes or arrangements that a molecule can adopt.

Conformations refer to the different ways that a molecule, such as a protein, can fold and arrange its atoms. These different conformations can affect the molecule's function.

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Folding@home

A distributed computing project that simulates protein folding.

Folding@home is a volunteer computing project that uses the processing power of donated computers to simulate protein folding. This helps researchers understand how proteins fold and function.