Molecular dynamics applied in drug discovery: the case of HIV-1 protease

Molecular dynamics (MD) is a way to computationally simulate the movement of particles and it is widely used to provide a dynamic perspective on biomolecules. Nowadays, the ever-growing computer power and the improvement in methodology further strengthen the role of MD in drug discovery. In this chapter, an overview of MD's application in drug discovery will be given first, using HIV-1 protease as an example. Then, the underlying theories of MD will be briefly outlined. The second half of this chapter will provide a practical protocol on how to simulate a soluble protein in solvent. All-atom simulation with either implicit solvent or explicit solvent will be covered. The former samples global conformational change more efficiently, and post-processing including angle/distance measurement, structural deviation measurement, Ramachandran plot, and secondary structure analysis will be introduced. The latter is more realistic/expensive and is generally used to finely examine local conformational rearrangement and water-mediated interactions. Post-processing including water density analysis will be described.