WITHDRAWN: Intrinsic Opening of BK Channels Derives from Inherent Leakage in Hydrophobic Gating

To design safe, selective, and effective new therapies, there must be a deep understanding of the structure and function of the drug target. One of the most difficult problems to solve has been resolution of discrete conformational states of transmembrane ion channel proteins. An example is KV11.1 (hERG), comprising the primary cardiac repolarizing current, IKr. hERG is a notorious drug anti-targe...

Biophysical characterization of protein structure and dynamics is essential in many scientific fields, including molecular biology, drug discovery, and enzyme design. Molecular dynamics (MD) simulations have become an increasingly important tool for studying these properties. This chapter provides a hands-on introduction to protein modeling with the Martini 3 coarse-grained (CG) force field. We ou...

Why does the same oncogenic mutation drive tumor formation in some tissues but not in others? While cancer driver mutations are well documented, their tissue specific effects remain largely attributed to genetic factors, leaving the biophysical aspects underexplored. Here, we demonstrate that mechanical interactions, specifically interfacial tension between newly transformed and wildtype epithelia...

Collagen IV is one of the main components of the basement membrane, a layer of material that lines the majority of tissues in multicellular organisms. Collagen-IV molecules assemble into networks, providing stiffness and elasticity to tissues and informing cell and organ shape, especially during development. In this work, we develop two coarse grained models for collagen-IV molecules that retain b...

Glycans on the cell surface play an essential role in mediating cell-cell interactions as well as immune response. Despite their importance, interactions between them have not been fully characterized. Here, we reveal, using all-atom molecular dynamics simulations and free energy calculations, that water-mediated interactions between a pair of N-glycans without net charge are weakly repulsive with...

The fundamental molecules of life are polymers. Prominent examples include nucleic acids and proteins, both of which exhibit a large array of mechanical properties and three-dimensional shapes. The bending rigidity of individual polymers is quantified by the persistence length. The shape of a polymer, dictated by the topology of the polymer backbone, a line trace through the center of the polymer ...

Exponential accumulation of cell size and highly expressed proteins is observed at the single-cell level in many bacterial species. While the exponential rates fluctuate from cycle to cycle, they remain stable on average over time and strongly correlated across different proteins and cell size. In this study, we investigate growth-rate variability at this state of \textit{balanced biosynthesis}, a...

We present Alpha-BET, a structure-guided strategy leveraging AlphaFold to identify optimal ALFAtag insertion sites for minimally disruptive labeling of viral glycoproteins with high-affinity nanobodies. Applied to HIV-1 Env, SARS-CoV-2 S, and Nipah G, Alpha-BET preserves structural integrity and function. For HIV-1 Env, we demonstrate super-resolution DNA-PAINT MINFLUX 3D imaging enabled by tag in...

The axolotl is a highly regenerative species, capable of restoring full limbs, regardless of the amputation site. However, the regeneration rate is adjusted with the plane of amputation along the proximo-distal (PD) axis, leading to equivalent regeneration times regardless of the extent of tissue removal. We hypothesized that this phenomenon could be partly explained by differences in tissue mecha...