NMR characterization of an assembling RHIM (RIP homotypic interaction motif) amyloid reveals a cryptic region for self-recognition.

The RIP homotypic interaction motif (RHIM) is an essential protein motif in inflammatory signaling and certain cell death pathways. RHIM signaling occurs following the assembly of functional amyloids, and while the structural biology of such higher-order RHIM complexes has started to emerge, the conformations and dynamics of nonassembled RHIMs remain unknown. Here, using solution NMR spectroscopy, we report the characterization of the monomeric form of the RHIM in receptor-interacting protein kinase 3 (RIPK3), a fundamental protein in human immunity.

Predicting protein stability changes upon mutation using a simple orientational potential.

Motivation: Structure-based stability prediction upon mutation is crucial for protein engineering and design, and for understanding genetic diseases or drug resistance events. For this task, we adopted a simple residue-based orientational potential that considers only three backbone atoms, previously applied in protein modeling. Its application to stability prediction only requires parametrizing 12 amino acid-dependent weights using cross-validation strategies on a curated dataset in which we tried to reduce the mutations that belong to protein-protein or protein-ligand interfaces, extreme conditions and the alanine over-representation.

Local Normal Mode Analysis for Fast Loop Conformational Sampling.

We propose and validate a novel method to efficiently explore local protein loop conformations based on a new formalism for constrained normal mode analysis (NMA) in internal coordinates. The manifold of possible loop configurations imposed by the position and orientation of the fixed loop ends is reduced to an orthogonal set of motions (or modes) encoding concerted rotations of all the backbone dihedral angles. We validate the sampling power on a set of protein loops with highly variable experimental structures and demonstrate that our approach can efficiently explore the conformational space of closed loops.

InterEvDock3: a combined template-based and free docking server with increased performance through explicit modeling of complex homologs and integration of covariation-based contact maps.

The InterEvDock3 protein docking server exploits the constraints of evolution by multiple means to generate structural models of protein assemblies. The server takes as input either several sequences or 3D structures of proteins known to interact. It returns a set of 10 consensus candidate complexes, together with interface predictions to guide further experimental validation interactively.

Phe-Gly motifs drive fibrillization of TDP-43's prion-like domain condensates.

Transactive response DNA-binding Protein of 43 kDa (TDP-43) assembles various aggregate forms, including biomolecular condensates or functional and pathological amyloids, with roles in disparate scenarios (e.g., muscle regeneration versus neurodegeneration).

Atomic-level evolutionary information improves protein-protein interface scoring.

Motivation: The crucial role of protein interactions and the difficulty in characterizing them experimentally strongly motivates the development of computational approaches for structural prediction. Even when protein-protein docking samples correct models, current scoring functions struggle to discriminate them from incorrect decoys. The previous incorporation of conservation and coevolution information has shown promise for improving protein-protein scoring.

KORP-PL: a coarse-grained knowledge-based scoring function for protein-ligand interactions.

Motivation: Despite the progress made in studying protein-ligand interactions and the widespread application of docking and affinity prediction tools, improving their precision and efficiency still remains a challenge. Computational approaches based on the scoring of docking conformations with statistical potentials constitute a popular alternative to more accurate but costly physics-based thermodynamic sampling methods. In this context, a minimalist and fast sidechain-free knowledge-based potential with a high docking and screening power can be very useful when screening a big number of putative docking conformations.

RNA binding proteins: Diversity from microsurgeons to cowboys.

The conformation and mechanism of proteins that degrade and bind RNA, which has provided key insights into post-transcriptional gene regulation, is explored here. During the twentieth century's last decades, the characterization of ribonucleases and RNA binding domains revealed the diversity of their reaction mechanisms and modes of RNA recognition, and the bases of protein folding, substrate specificity and binding affinity. More recent research showed how these domains combine through oligomerization or genetic recombination to create larger proteins with highly specific and readily programmable ribonucleolytic activity.

KORP: knowledge-based 6D potential for fast protein and loop modeling.

Motivation: Knowledge-based statistical potentials constitute a simpler and easier alternative to physics-based potentials in many applications, including folding, docking and protein modeling. Here, to improve the effectiveness of the current approximations, we attempt to capture the six-dimensional nature of residue-residue interactions from known protein structures using a simple backbone-based representation.

Results: We have developed KORP, a knowledge-based pairwise potential for proteins that depends on the relative position and orientation between residues.

Influence of the light source and bleaching gel on the efficacy of the tooth whitening process.

Objective: To examine the whitening efficacy of three whitening agents in combination with six different photoactivation systems.

Background: Bleaching techniques have achieved significant advances using photoactivation with coherent or incoherent radiation sources.

Methods: Quick White, Ena White Power, and Opalescence Endo bleaching agents, all containing 35% hydrogen peroxide, were stimulated with halogen lamp, light-emitting diode (LED), low-power diode laser, and neodymium: yttrium-aluminum-garnet (Nd:YAG), second harmonic of Nd:YAG, and Er:YAG lasers.