Molecular dynamic simulations for studying biological macromolecules

You may be wondering why I am starting my bioinformatics blog with a topic like this! rather than starting with an Introduction to bioinformatics or sequence analysis. This was the topic which interested me a lot and I couldn’t wait to watch my first molecular dynamic simulation movie. I was so excited and happy to see the movement of my protein, to observe how the active site pocket changes its conformation, how some loops gating the pocket beautifully helps in opening or closing the active site pocket. But theoretically, it was very difficult to understand for me in the beginning. All I could find in the textbooks and n number of resources in internet was a number of equations and algorithms, some complicated differential equations and it really scared me.

U maybe wondering like me! Is it really necessary for me to know the theory? Can’t I just learn how to use the software to generate a simulation of my interest? U can go straight to watching some tutorials on how to do a simulation and do but, those tutorials will not be helpful with whatever macro molecule you want to study in your research. You cannot perform every simulation with the parameters given in that sample protein. You will need to set up a different system and change parameters every time depending on what you want to study and your macro molecule of interest whether it is a protein or nucleic acid. Therefore it is necessary to understand the basics, get some background knowledge about MD simulations, why you need to use a particular algorithm or choose a particular force field, etc. I am presenting a very simplified explanation of MD simulations for biologists so that it is easy to understand without much equations and derivations. So here we go!!

 

What is  Molecular dynamic simulation?

Before going to molecular dynamic simulation, what do you understand by simulation? Most of us have come across simulations. We have even seen or used some form of computer simulations, watched a 5D movie of a roller coaster, different games we play in our phones are simulations that mimic real world.  We also use simulations for different learning purpose like in a driving school, military training, astronaut training or the use of anatomy simulation tools in medicine.

A simulation is an imitation of the real world process or system. This is done by building a model. If you have to build a model of a real system, we should first understand the characteristics, properties and features of the real system. We never build a simulation. We build a model and we run a model. In order to model a system with computers we should give a set of instructions for the computers. A computer model is the set of algorithms and equations used to capture the behaviour of the system.  The term computer simulation is the actually the process of running of the program.

In general, the process of building a computer model is by trial and error. We first build a model after careful study of real system and perform simulation on the model and then compare the results against experimental results obtained from the real system. We study the results and see how well the model is similar to the real system. Until, similar results are obtained in both we would continue to make modifications to the computer algorithm and improve the model.

So, what is MD simulation...?

Let’s split this term to understand its meaning. The adjective molecular describes that we are going to look at things in the molecular level. We know that molecules are a group of atoms connected by chemical bonds as biologist, we talk about biomolecules like proteins, lipids etc. Dynamics is the study of forces and their effect on motion. Or simply study of movement .Thereby in molecular dynamics we are going to study about the movement of molecules. Lastly, simulation is an imitation of the real world process/system; it is an abstraction of the real world. So, Molecular dynamics simulation (MD) is a computer simulation method for studying the physical movements of atoms and molecules

In molecular dynamic simulation, the atoms and molecules are allowed to interact for a fixed period of time, the movement/ trajectories of atoms and molecules are determined by numerically solving Newton's equations of motion. The method was originally developed within the field of theoretical physics in the late 1950s.  But is applied today mostly in chemical physics, materials science and the modelling of biomolecules

MD is like a computational experiment where a system is defined, allowed to evolve, and then observations made based on its evolution.


Now I am going to introduce an important term.  A term that is widely used in Molecular dynamics simulations: “Force field”. Force Field is the functional form and parameter sets used to calculate the Potential Energy of a system of atoms. It is also called as the Potential Energy function

Force fields are chosen according to the computational experiment needs. Force-fields currently used in molecular simulations differ in the way they are parameterized not all force-fields allow to represent all molecule types. Suppose, you need to perform simulation of a protein with a Zn ion you need to choose force field that has taken this atom into consideration. We will know more about the force field in the upcoming blog.

Molecular dynamics (MD) simulation is a computational tool used to describe how positions, velocities, and orientations of molecules change over time. The basic idea!  Mimic what atoms do in real life, assuming a given potential energy function (Force Field).

I will continue to talk about molecular dynamics application, steps in the future blog.

Watch the video and subscribe to the youtube channel to learn more !