FlowBack: A Generalized Flow-Matching Approach for Biomolecular Backmapping.

Coarse-grained models have become ubiquitous in biomolecular modeling tasks aimed at studying slow dynamical processes such as protein folding and DNA hybridization. These models can considerably accelerate sampling but it remains challenging to accurately and efficiently restore all-atom detail to the coarse-grained trajectory, which can be vital for detailed understanding of molecular mechanisms and calculation of observables contingent on all-atom coordinates. In this work, we introduce FlowBack as a deep generative model employing a flow-matching objective to map samples from a coarse-grained prior distribution to an all-atom data distribution.

Thermodynamics and kinetics of DNA and RNA dinucleotide hybridization to gaps and overhangs.

Hybridization of short nucleic acid segments (<4 nt) to single-strand templates occurs as a critical intermediate in processes such as nonenzymatic nucleic acid replication and toehold-mediated strand displacement. These templates often contain adjacent duplex segments that stabilize base pairing with single-strand gaps or overhangs, but the thermodynamics and kinetics of hybridization in such contexts are poorly understood because of the experimental challenges of probing weak binding and rapid structural dynamics. Here we develop an approach to directly measure the thermodynamics and kinetics of DNA and RNA dinucleotide dehybridization using steady-state and temperature-jump infrared spectroscopy.

Direct monitoring of the thermodynamics and kinetics of DNA and RNA dinucleotide dehybridization from gaps and overhangs.

Hybridization of short nucleic acid segments (<4 nucleotides) to single-strand templates occurs as a critical intermediate in processes such as non-enzymatic nucleic acid replication and toehold-mediated strand displacement. These templates often contain adjacent duplex segments that stabilize base pairing with single-strand gaps or overhangs, but the thermodynamics and kinetics of hybridization in such contexts are poorly understood due to experimental challenges of probing weak binding and rapid structural dynamics. Here we develop an approach to directly measure the thermodynamics and kinetics of DNA and RNA dinucleotide dehybridization using steady-state and temperature-jump infrared spectroscopy.