Molecular Simulation
Molecular simulation is a physics-based modelling approach. We set up in the computer a mathematical representation of the molecules involved, one that typically includes the chemical nature and spatial co-ordinates of each constituent atom. The computer then produces a possible future of that molecular system, calculating its response to its physical and chemical environment at each timestep to create a trajectory, in a process known as Molecular Dynamics.
If carried out intelligently, such methods can provide great scientific insight into the behaviour of the system, covering things such as structure, energy, interactions with other molecules, phase changes and much more. Typically, simulations are carried out with the molecules contained in 3-dimensional boxes that are stacked together without limit in all directions and fill space with no gaps, a scenario described as having “periodic boundary conditions.” Our group use such methods for structural studies of the interactions between enzymes and their substrates, with applications like plastic-eating enzymes and new medicines.
The forces, or more explicitly the interaction energies, between molecules are defined by a “force field”, which has little to do with science fiction but a lot to do with the fundamental physical processes governing the attractive and repulsive interactions amongst atoms and molecules. This forms a major part of the scientific input into simulations. Historically, force fields have been either fitted to experiment or parameterised via theoretical calculation, but increasingly they are now being generated through ML.
While techniques such as Molecular Dynamics have benefitted greatly from increases in computer power, they are fundamentally based on 20th century science and the way forward for the field is unclear. It’s likely that Machine Learning will have a big influence on the future of simulation, one way or another.
Our Recent Publication in Molecular Simulation
Shrimpton-Phoenix, E., Mitchell, J. B. O. & Buehl, M., Computational insights into the catalytic mechanism of is-PETase: an enzyme capable of degrading poly(ethylene) terephthalate, Chemistry – A European Journal, 28, (70): e202201728, https://10.1002/chem.202201728