Can molecular dynamics be used to simulate biomolecular recognition?

Malin Liking, David van der Spoel, Johan Elf, Gareth Tribello*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


There are many problems in biochemistry that are difficult to study experimentally. Simulation methods are appealing due to direct availability of atomic coordinates as a function of time. However, direct molecular simulations are challenged by the size of systems and the time scales needed to describe relevant motions. In theory, enhanced sampling algorithms can help to overcome some of the limitations of molecular simulations. Here, we discuss a problem in biochemistry that offers a significant challenge for enhanced sampling methods and that could, therefore, serve as a benchmark for comparing approaches that use machine learning to find suitable collective variables. In particular, we study the transitions LacI undergoes upon moving between being non-specifically and specifically bound to DNA. Many degrees of freedom change during this transition and that the transition does not occur reversibly in simulations if only a subset of these degrees of freedom are biased. We also explain why this problem is so important to biologists and the transformative impact that a simulation of it would have on the understanding of DNA regulation.
Original languageEnglish
Article number184106
JournalJournal of Chemical Physics
Early online date09 May 2023
Publication statusPublished - 14 May 2023


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