RESEARCH: FORCE-FIELD-PROTEIN-DYNAMICS
FOLDING PROJECT #18235 PROFILE

This project studies how well different computer models simulate the behavior of proteins like lysozyme. They use a protein called T4 Lysozyme because scientists have already studied it a lot. The goal is to improve these computer models so they can accurately predict how proteins fold and function, which is important for understanding diseases and developing 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 18239- Amber99SB-star-ILDN with TIP4PD water 18240- Amber99SB-disp with TIP4PD-1.6 water.

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Force fields

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

Force fields are mathematical models used in molecular dynamics simulations to describe the interactions between atoms. They are essential for accurately simulating the movement and behavior of molecules.

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Molecular Dynamics

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

Molecular dynamics simulations use computer algorithms to model the behavior of atoms and molecules over time. This allows scientists to study how molecules interact and move, which is essential for understanding biological processes and designing new drugs.

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Newton's laws of motion

Fundamental principles that govern the motion of objects.

Newton's laws of motion describe how forces affect the motion of objects. These laws are essential for understanding a wide range of phenomena, from the motion of planets to the behavior of everyday objects.

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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. In molecular dynamics simulations, femtoseconds represent the small time steps taken to update the positions and velocities of atoms.

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Protein

A large biological molecule composed of amino acids.

Proteins are essential molecules that perform a wide variety of functions in living organisms. They are involved in everything from catalyzing biochemical reactions to transporting molecules across cell membranes.

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Lysozyme

An enzyme that breaks down bacterial cell walls.

Lysozyme is an antibacterial enzyme found in many organisms, including humans. It plays a crucial role in the immune system by breaking down the cell walls of bacteria.

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Folding@home

A distributed computing project that uses volunteer computer time to simulate protein folding.

Folding@home is a large-scale computing project that harnesses the power of thousands of volunteer computers to simulate how proteins fold. These simulations help researchers understand the complex process of protein folding and its role in disease.