RESEARCH: MOLECULAR-DYNAMICS-FORCE-FIELDS
FOLDING PROJECT #18244 PROFILE

This project tests different computer models used to simulate how atoms in proteins move. They use a well-studied protein called lysozyme to see how accurate each model is. The goal is to improve these models so scientists can better understand 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 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 collective model describing how to calculate forces on atoms in a molecular dynamics simulation.

Force fields are computational models used in molecular dynamics simulations to describe the interactions between atoms. They are essential for accurately simulating the behavior of molecules, such as proteins and DNA.

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Molecular Dynamics Simulations

Computer simulations that model the motion of atoms and molecules over time.

Molecular dynamics simulations are a powerful tool for studying the behavior of molecules. They work by simulating the movement of atoms and molecules according to the laws of physics. This allows scientists to understand how molecules interact with each other and their environment.

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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 movement of objects. They are fundamental to understanding the physical world and are used in many different fields, including engineering and astronomy.

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Femtoseconds

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

Femtoseconds are incredibly short units of time. They are used to measure the extremely fast processes that occur in atoms and molecules.

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Proteins

Large, complex molecules that play many essential roles in living organisms.

Proteins are the workhorses of cells, carrying out a vast array of functions. They are made up of chains of amino acids and fold into specific shapes that allow them to perform their tasks.

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T4 Lysozyme

An enzyme that breaks down bacterial cell walls.

T4 Lysozyme is a well-studied enzyme that plays an important role in the immune system. It is used to study how proteins fold and function.

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Folding@home

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

Folding@home is a scientific research project that harnesses the power of thousands of computers to simulate the complex process of protein folding. This helps scientists understand how proteins work and develop new drugs.