Unexplored regions of the protein sequence-structure map revealed at scale by a library of foldtuned language models.

Nature has likely sampled only a fraction of all protein sequences and structures allowed by the laws of biophysics. However, the combinatorial scale of amino-acid sequence-space has traditionally precluded substantive study of the full protein sequence-structure map. In particular, it remains unknown how much of the vast uncharted landscape of far-from-natural sequences consists of alternate ways to encode the familiar ensemble of natural folds; proteins in this category also represent an opportunity to diversify candidates for downstream applications.

Pulsed Nano-ESI Atmospheric-Pressure Ion Mobility Mass Spectrometry with Enhanced Ion Sampling.

Ion mobility-mass spectrometry (IM-MS) has gained considerable attention for detection of clusters and weakly bound species created by electrospray ionization (ESI). Atmospheric-pressure (AP) IM-MS offers an advantage in these studies compared to its low-pressure counterpart, owing to soft introduction of ions into the mobility cell with minimal ion activation. Here, we report new approaches to improve the sensitivity and soft ion introduction in AP-IM-MS.