Computational Prediction of Intrinsically Disordered Proteins Based on Protein Sequences and Convolutional Neural Networks

Intrinsically disordered proteins (IDPs) possess at least one region that lacks a single stable structure in vivo, which makes them play an important role in a variety of biological functions. We propose a prediction method for IDPs based on convolutional neural networks (CNNs) and feature selection. The combination of sequence and evolutionary properties is used to describe the differences between disordered and ordered regions. Especially, to highlight the correlation between the target residue and adjacent residues, multiple windows are selected to preprocess the protein sequence through the selected properties. The shorter windows reflect the characteristics of the central residue, and the longer windows reflect the characteristics of the surroundings around the central residue. Moreover, to highlight the specificity of sequence and evolutionary properties, they are preprocessed, respectively. After that, the preprocessed properties are combined into feature matrices as the input of the constructed CNN. Our method is training as well as testing based on the DisProt database. The simulation results show that the proposed method can predict IDPs effectively, and the performance is competitive in comparison with IsUnstruct and ESpritz.

Glycine in Water Favors the Polyproline II State

Conformational preferences of amino acid residues in water are determined by the backbone and side-chain properties. Alanine is known for its high polyproline II (pPII) propensity. The question of relative contributions of the backbone and side chain to the conformational preferences of alanine and other amino acid residues in water is not fully resolved. Because glycine lacks a heavy-atom side chain, glycine-based peptides can be used to examine to which extent the backbone properties affect the conformational space. Here, we use published spectroscopic data for the central glycine residue of cationic triglycine in water to demonstrate that its conformational space is dominated by the pPII state. We assess three commonly used molecular dynamics (MD) force fields with respect to their ability to capture the conformational preferences of the central glycine residue in triglycine. We show that pPII is the mesostate that enables the functional backbone groups of the central residue to form the most hydrogen bonds with water. Our results indicate that the pPII propensity of the central glycine in GGG is comparable to that of alanine in GAG, implying that the water-backbone hydrogen bonding is responsible for the high pPII content of these residues.

Set-theoretic solutions to the Yang–Baxter equation, skew-braces, and related near-rings

Skew-braces have been introduced recently by Guarnieri and Vendramin. The structure group of a non-degenerate solution to the Yang–Baxter equation is a skew-brace, and every skew-brace gives a set-theoretic solution to the Yang–Baxter equation. It is proved that skew-braces arise from near-rings with a distinguished exponential map. For a fixed skew-brace, the corresponding near-rings with exponential form a category. The terminal object is a near-ring of self-maps, while the initial object is a near-ring which gives a complete invariant of the skew-brace. The radicals of split local near-rings with a central residue field [Formula: see text] are characterized as [Formula: see text]-braces with a compatible near-ring structure. Under this correspondence, [Formula: see text]-braces are radicals of local near-rings with radical square zero.

The use of 4,4,4-trifluorothreonine to stabilize extended peptide structures and mimic β-strands

Pentapeptides having the sequence R-HN-Ala-Val-X-Val-Leu-OMe, where the central residue X is L-serine, L-threonine, (2S,3R)-L-CF3-threonine and (2S,3S)-L-CF3-threonine were prepared. The capacity of (2S,3S)- and (2S,3R)-CF3-threonine analogues to stabilize an extended structure when introduced in the central position of pentapeptides is demonstrated by NMR conformational studies and molecular dynamics simulations. CF3-threonine containing pentapeptides are more prone to mimic β-strands than their natural Ser and Thr pentapeptide analogues. The proof of concept that these fluorinated β-strand mimics are able to disrupt protein–protein interactions involving β-sheet structures is provided. The CF3-threonine containing pentapeptides interact with the amyloid peptide Aβ1-42 in order to reduce the protein–protein interactions mediating its aggregation process.

A 2:1 co-crystal of 2-methylbenzoic acid andN,N′-bis(pyridin-4-ylmethyl)ethanediamide: crystal structure and Hirshfeld surface analysis

The asymmetric unit of the title 2:1 co-crystal, 2C8H8O2·C14H14N4O2, comprises an acid molecule in a general position and half a diamide molecule, the latter being located about a centre of inversion. In the acid, the carboxylic acid group is twisted out of the plane of the benzene ring to which it is attached [dihedral angle = 28.51 (8)°] and the carbonyl O atom and methyl group lie approximately to the same side of the molecule [hydroxy-O—C—C—C(H) torsion angle = −27.92 (17)°]. In the diamide, the central C4N2O2core is almost planar (r.m.s. deviation = 0.031 Å), and the pyridyl rings are perpendicular, lying to either side of the central plane [central residue/pyridyl dihedral angle = 88.60 (5)°]. In the molecular packing, three-molecule aggregates are formedviahydroxy-O—H...N(pyridyl) hydrogen bonds. These are connected into a supramolecular layer parallel to (12\overline{2})viaamide-N—H...O(carbonyl) hydrogen bonds, as well as methylene-C—H...O(amide) interactions. Significant π–π interactions occur between benzene/benzene, pyridyl/benzene and pyridyl/pyridyl rings within and between layers to consolidate the three-dimensional packing.

Discovery of a low affinity thyrotropin-releasing hormone (TRH)-like peptide that exhibits potent inhibition of scopolamine-induced memory impairment in mice

TRH-like peptides were synthesized in which the critical N-terminus residuel-pGlu was replaced with various heteroaromatic rings, and the central residue histidine with 1-alkyl-l-histidines.

O-Propyl N-phenylthiocarbamate

Two independent molecules comprise the asymmetric unit in the title thiocarbamide derivative, C10H13NOS. These differ in the relative orientations of terminal ethyl groups [C—C—C—O torsion angles = −66.95 (13) and 55.92 (13)°, respectively]. The phenyl ring is twisted out of the plane of the central residue [Cq—N—Cph—Cph = −146.20 (12) and −144.15 (12)°, respectively; q = quaternary and ph = phenyl]. The independent molecules are linked into a dimeric aggregate by N—H...S hydrogen bonds and an eight-membered thioamide {...H—N—C=S}2 synthon.