Molecular Dynamics simulations: concepts and applications
Characterization of biomolecular structures under different conditions is a key point in order to establish a proper comprehension of the interactions between them. This contributes to the development of drugs, therapies, and techniques that help cure diseases. However, under real-time laboratory conditions, it is impossible to precisely calculate the time-dependent behavior of biological molecules. Moreover, biological samples are quite expensive. All of this can lead us away from understanding the complex dynamic biological processes such as enzymatic reactions, protein stability, folding, conformational changes, etc. However, simulations help us to avoid this problem by using computational techniques.? ?
Until as late as the 1950s, the simulation of biological molecules was kind of unknown. But after the series of discoveries, it became one of the hottest topics in the research world. Molecular Dynamics (MD) simulation is a widely used approach that allows us to estimate the dynamicity of molecules by the interaction of atoms and molecules for a secure period of time. ?
This method provides information about structures, conformational changes, dynamics, and thermodynamics of molecules by analyzing their movement and chemical interactions. MD saves time and effort and the fact that further experimentation is done on the screened molecules only, there is a much higher chance of getting positive and desired results. ?
There are two types of simulation techniques – Monte Carlo and Molecular Dynamic simulation. What sets them apart is that Monte Carlo simulations are preferable for a low-density system, like gas, while MD simulations are chosen for liquids. The basic idea of MD is to calculate the forces exerted on each atom in the biomolecular system by all other atoms, assuming that the positions of all atoms are known. Thus, we can predict the spatial position of each atom as a function of time using Newton’s laws of motion. ?
These simulations are powerful for several reasons. Firstly, they provide a comprehensive account of the position and movement of each atom at every moment, a feat that proves challenging for experimental methods. Secondly, the simulation conditions are well-defined and can be meticulously regulated. This includes factors like the initial configuration of a protein, the presence of ligands, potential mutations, or post-translational modifications.?
So molecular dynamics?as a part of structure-based drug design plays a crucial role in modern drug discovery campaigns. It can be used to obtain a set of protein conformations for molecular docking and thus incorporate some level of target flexibility. Moreover, by analyzing MD trajectories of protein-ligand complexes one may obtain some insights into their behavior, and stability, investigate interactions that occur during the simulation, etc. However, the most exciting utilization of MD is a calculation of absolute or relative binding free energies that can be used, for instance, in lead optimization of promising compounds.
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