RESEARCH: FORCE-FIELD-PROTEIN-DYNAMICS
FOLDING PROJECT #18240 PROFILE

This project uses computer simulations to study how proteins move and change shape. They're testing different models (like force fields) to see which one best predicts how a protein called T4 Lysozyme behaves. This helps scientists understand how proteins work and could lead to better drugs and treatments.

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.

---

Force fields

A model used in molecular dynamics simulations to describe the interactions between atoms.

Force fields are mathematical models that represent how atoms interact with each other. They are essential for simulating the behavior of molecules in computer programs, allowing scientists to study things like protein folding and drug interactions.

---

Molecular dynamics simulations

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

Molecular dynamics simulations use computer programs to imitate how atoms and molecules interact. They help scientists understand how proteins fold, how drugs bind to targets, and other complex biological processes.

---

Newton's laws of motion

Fundamental principles that describe the relationship between force, mass, and motion.

Newton's laws of motion are the foundation of classical mechanics. They explain how objects move and interact based on forces acting upon them.

---

Atoms

The basic building blocks of all matter.

Atoms are the smallest units of an element that retain its chemical properties. They consist of a nucleus containing protons and neutrons, surrounded by orbiting electrons.

---

Proteins

Large biomolecules essential for a wide range of biological functions.

Proteins are complex molecules made up of amino acids. They play crucial roles in nearly every aspect of life, including catalyzing reactions, transporting molecules, and providing structural support.

---

Force field/water combinations

Specific sets of parameters used in molecular dynamics simulations to describe the interactions between atoms and water molecules.

Force fields are mathematical models that represent how atoms interact. When simulating biomolecules, it's crucial to also account for the interaction with surrounding water molecules. Force field/water combinations specify these interactions, ensuring a realistic simulation.

---

T4 Lysozyme

A well-studied protein with antibacterial properties.

T4 Lysozyme is an enzyme found in bacteriophages (viruses that infect bacteria). It plays a vital role in breaking down bacterial cell walls, making it a target for studying protein function and design.

---

Folding@home

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

Folding@home harnesses the power of many computers worldwide to simulate how proteins fold. This helps researchers understand the complex process of protein structure formation and its implications for disease.