The “RNA world” hypothesis poses that a crucial step in the origin of life was the spontaneous emergence of RNA molecules capable of catalyzing their own copying. Recently, experiments identified an exceptionally short RNA strand with self-copying capabilities, named QT45 (https://doi.org/10.1126/science.adt2760). The fact that the QT45 sequence is so short fundamentally shifts our perspective on pre-biotic scenarios, as a shorter strand has a higher probability of forming by chance, providing a plausible starting point for the emergence of life. Unraveling the exact mechanisms behind QT45 replication could offer vital insights into alternative RNA replicators and early prebiotic pathways.
Molecular simulation can reveal, with atomistic detail, key features of the QT45 sequence that facilitate each step of the replication process. However, QT45 functions as a replicator only in very cold, salt-crowded conditions where chemical reactions and conformational changes occur at prohibitively slow timescales for standard simulations. Luckily, a variety of enhanced sampling algorithms and machine learning approaches can be used to drive the process and accelerate simulations.
In this project, you will implement advanced molecular simulation methods to reveal key steps in the replication of the QT45 RNA sequence. Depending on your interests, you may focus on specific critical steps—e.g., the binding of complementary nucleotides, the polymerization of the new strand, or the unbinding and copying of the newly formed sequence. Experience with molecular simulation is desirable.
