The latest Interface Focus issue focuses on multi-resolution simulations of intracellular processes. The issue provides a ‘snapshot’ of an area of research that aims to address the computational challenges associated with simulating large collections of biomolecules over system-level time scales efficiently. We spoke with one of the organisers of the issue, Professor Radek Erban from the University of Oxford, to learn more.
Why are computer-aided studies important in life sciences?
The behaviour of a living cell depends on the interactions between individual biomolecules, from which the cell is made. Even relatively simple bacteria can include thousands of different genes and proteins, and building computational models can help us to understand the underlying details of their interactions.
Larger cells (e.g. human cells) are even more complex, and good computational models can not only tell us how the cell functions in health and disease, but also how changes at the molecular-level could lead to desired changes (therapy, treatment) of cell-level properties.
What is the aim of this Interface Focus issue?
The physics of cells is so complex to model computationally because of the need to bridge multiple theoretical regimes from quantum chemistry, such as enzyme catalysis, all the way up to the macroscopic time and length-scales associated with cell division.
This issue provides a snapshot of a research area that addresses computational challenges to efficiently simulate large collections of biomolecules over system-level time scales. For example, in some applications, microscopic detail is only required in a relatively small region (e.g. close to a cell membrane or a particular organelle).
One way to achieve this detail would be to use a computationally intensive model over the whole simulation domain (cell), but this is often computationally prohibitive. A better way is to develop and implement multi-resolution algorithms that efficiently and accurately couple molecular-based models with less-detailed (coarse-grained) modelling descriptions.
What are the challenges of this research area?
Arguably, classical molecular dynamics is the most established tool for the simulation of biological systems at the molecular level. However, molecular dynamics simulations are limited to relatively small systems containing thousands or millions of atoms, while a typical living cell is made of many more – trillions of atoms.
The challenge is thus to understand what is necessary to describe by a detailed molecular dynamics approach, and what can be left out, or described by a coarser model. Other current challenges of this research community are related to sharing computed data, and they are discussed in detail in the opinion article in the theme issue written by Riccardi, Pantano, and Potestio (2019).
“Molecular dynamics simulations are limited to relatively small systems containing thousands or millions of atoms, while a typical living cell is made of many more – trillions of atoms.”
What role does machine learning play in computer-based studies?
It complements the development of algorithms in this research area. While one challenge is to build predictive mathematical models, and the other is to efficiently simulate them on a computer, these computational studies produce a lot of data, and the further challenge is to extract useful information stored in the computed data. This issue of Interface Focus includes papers using machine-learning approaches to analyse computed molecular structures and dynamical trajectories.
What is the future for the use of computational methods in life sciences?
This issue of Interface Focus contains papers authored by speakers of the Theo Murphy International Scientific Meeting on “Multi-resolution simulations of intracellular processes”, which was held at the Kavli Royal Society Centre in Chicheley Hall (United Kingdom) on September 24-25, 2018.
A number of future directions have been discussed during this meeting. The future lies in simulating larger and more complex systems than we currently do. During the meeting, the largest systems presented included molecular dynamics studies of viruses, and this issue of Interface Focus presents a simulation of the whole virus capsid by Farafonov and Nerukh (2019). A further increase of the size of studied intracellular systems will be made possible by an interplay between the development of new multi-resolution algorithms, improvement of hardware and collaborative data sharing approaches.
“The future lies in simulating larger and more complex systems than we currently do.”