How do we study the dynamics of molecules?

Molecular dynamics will depend from the interaction between each atom composing a molecule and since molecules are tiny, their dynamics is very sensitive to microenvironmental conditions such as temperature, pressure, solvent conditions, salts, the presence of other molecules in solutions and much more.
The study of macromolecular dynamics therefore needs to consider all these factors.
Using computers we calculate the force acting between each particle composing a molecules and therefore solve molecular dynamics.

The forces between particles will change as a function of their position. A descriptor of how the interaction energy between two particles changes as a function of their distance is given by a force field.
Force fields are therefore a collection of equations and parameters that define the interaction between particle pairs.

The simplest description of a molecular dynamics algorithm

From a static structure, usually retrieved by experimental means, we assign random velocities to the particles and predict their next positions considering a time step (Δt). We then compute forces using the parameters defined in the force field. We correct particle positions and velocities according to the computed forces and update the time. Repeating these simple steps multiple times literally provides a molecular movie where the positions of each particle composing a system are integrated over time. From a molecular dynamics trajectory is then possible to compute any physical quantity, using this high-resolution picture of the investigated molecule.

Why molecular dynamics simulations perfectly complement experiments.

Most experimental methods that aim at solving the structure of macro-molecules greatly benefit by a low amount of fluctuations.
More a molecule is static, better our ability to define the position of its atoms in space becomes. It’s like taking a picture of a subject that either stands still or moves while the picture is being taken. It is obvious that pictures taken on moving subjects are going to be blurry!
Therefore, experimental methods mostly obtain high resolution from static images of molecules, which, as explained above, only partially describe their ability to perform a function.
Molecular simulations overcome this because, given a certain structure, can re-obtain dynamics by sampling the interactions between each of its composing units.
Therefore, beyond structure, they can complement experiments by providing the missing dynamics.

In our lab, we reconstruct dynamics of molecules by using a diverse set of computational strategies and ultimately comparing our findings with the ones coming from experiments in a highly multidisciplinary environment.
Our microscope is the computer, which allow us to obtain a lot of information at once.

By simulating the dynamics of a molecule, we can:
• Understand its function.
• Understand how the interaction with other molecules regulates its function.
• Design new molecules with enhanced function.
• Design strong binders for known macromolecules that we aim to target.
• Predict the properties of molecules in different micro-environmental conditions.

By providing a highly detailed molecular picture of the dynamics-linked process involving the investigated molecules, molecular simulations greatly increase the resolution range of experiments. They help formulating new hypothesis by predicting molecular behaviour and have a crucial role for formulating new strategies to tackle scientific problems.
This is why experiments and simulations can be perfectly coupled, to ultimately access scientific excellence.

“It is far better to foresee even without certainty, than not to foresee at all”.
Henri Poincare, The Foundation of Science. 1929.