AlphaFold predicts novel human proteins with knots.

The fact that proteins can have their chain formed in a knot is known for almost 30 years. However, as they are not common, only a fraction of such proteins is available in the Protein Data Bank. It was not possible to assess their importance and versatility up until now because we did not have access to the whole proteome of an organism, let alone a human one. The arrival of efficient machine learning methods for protein structure prediction, such as AlphaFold and RoseTTaFold, changed that. We analyzed all proteins from the human proteome (over 20,000) determined with AlphaFold in search for knots and found them in less than 2% of the structures. Using a variety of methods, including homolog search, clustering, quality assessment, and visual inspection, we determined the nature of each of the knotted structures and classified it as either knotted, potentially knotted, or an artifact, and deposited all of them in a database available at: https://knotprot.cent.uw.edu.pl/alphafold. Overall, we found 51 credible knotted proteins (0.2% of human proteome). The set of potentially knotted structures includes a new complex type of a knot not reported in proteins yet. That knot type, denoted 63 in mathematical notation, would necessitate a more complex folding path than any knotted protein characterized to date.

Sedimenting pairs of elastic microfilaments.

The dynamics of two identical elastic filaments settling under gravity in a viscous fluid in the low Reynolds number regime is investigated numerically. A large family of initial configurations symmetric with respect to a vertical plane is considered, as well as their non-symmetric perturbations. The behaviour of the filaments is primarily governed by the elasto-gravitational number, which depends on the filament's length and flexibility, and the strength of the external force. Flexible filaments usually converge toward horizontal and parallel orientation. We explain this phenomenon and show that it occurs also for curved rigid particles of similar shapes. Once aligned, the two fibres either converge toward a stationary, flexibility-dependent distance, or tend to collide or continuously repel each other. Rigid and straight rods perform periodic motions while settling down. Apart from very stiff particles, the dynamics is robust to non-symmetric perturbations.

Stokes velocity generated by a point force in various geometries.

In this short review, we visualize the fluid velocity generated by a point force close to a plane free surface or a plane rigid wall. We present separately contributions from all the multipoles which form the corresponding classical systems of images. Such graphical images might be useful in the theoretical and numerical modeling of the dynamics of micro-objects moving close to an interface.

Different bending models predict different dynamics of sedimenting elastic trumbbells.

The main goal of this paper is to examine theoretically and numerically the impact of a chosen bending model on the dynamics of elastic filaments settling in a viscous fluid under gravity at low-Reynolds-number. We use the bead-spring approximation of a filament and the Rotne-Prager mobility matrix to describe hydrodynamic interactions between the beads. We analyze the dynamics of trumbbells, for which bending angles are typically larger than for thin and long filaments. Each trumbbell is made of three beads connected by springs and it exhibits a bending resistance, described by the harmonic or - alternatively - by the 'cosine' (also called the Kratky-Porod) bending models, both often used in the literature. Using the harmonic bending potential, and coupling it to the spring potential by the Young's modulus, we find simple benchmark solutions: stable stationary configurations of a single elastic trumbbell and attraction of two elastic trumbbells towards a periodic long-lasting orbit. As the most significant result of this paper, we show that for very elastic trumbbells at the same initial conditions, the Kratky-Porod bending potential can lead to qualitatively and quantitatively different spurious dynamics, with artificially large bending angles and unrealistic shapes. We point out that for the bead models of an elastic filament, the range of applicability of the Kratky-Porod model might not go beyond bending angles smaller than π/2 for touching beads and beyond an even much lower value for beads well-separated from each other. The existence of stable stationary configurations of elastic trumbbells and a family of periodic oscillations of two elastic trumbbells are very important findings on their own.

High rates of phasing errors in highly polymorphic species with low levels of linkage disequilibrium.

Short read sequencing of diploid individuals does not permit the direct inference of the sequence on each of the two homologous chromosomes. Although various phasing software packages exist, they were primarily tailored for and tested on human data, which differ from other species in factors that influence phasing, such as SNP density, amounts of linkage disequilibrium (LD) and sample sizes. Despite becoming increasingly popular for other species, the reliability of phasing in non-human data has not been evaluated to a sufficient extent. We scrutinized the phasing accuracy for Drosophila melanogaster, a species with high polymorphism levels and reduced LD relative to humans. We phased two D. melanogaster populations and compared the results to the known haplotypes. The performance increased with size of the reference panel and was highest when the reference panel and phased individuals were from the same population. Full genomic SNP data and inclusion of sequence read information also improved phasing. Despite humans and Drosophila having similar switch error rates between polymorphic sites, the distances between switch errors were much shorter in Drosophila with only fragments <300-1500 bp being correctly phased with ≥95% confidence. This suggests that the higher SNP density cannot compensate for the higher recombination rate in D. melanogaster. Furthermore, we show that populations that have gone through demographic events such as bottlenecks can be phased with higher accuracy. Our results highlight that statistically phased data are particularly error prone in species with large population sizes or populations lacking suitable reference panels.

Periodic and quasiperiodic motions of many particles falling in a viscous fluid.

The dynamics of regular clusters of many nontouching particles falling under gravity in a viscous fluid at low Reynolds number are analyzed within the point-particle model. The evolution of two families of particle configurations is determined: two or four regular horizontal polygons (called "rings") centered above or below each other. Two rings fall together and periodically oscillate. Four rings usually separate from each other with chaotic scattering. For hundreds of thousands of initial configurations, a map of the cluster lifetime is evaluated in which the long-lasting clusters are centered around periodic solutions for the relative motions, and they are surrounded by regions of chaotic scattering in a similar way to what was observed by Janosi et al. [Phys. Rev. E. 56, 2858 (1997)] for three particles only. These findings suggest that we should consider the existence of periodic orbits as a possible physical mechanism of the existence of unstable clusters of particles falling under gravity in a viscous fluid.