Osmolyte-induced protein stability changes explained by graph theory.

Enhanced stabilization of protein structures via the presence of inert osmolytes is a key mechanism adopted both by physiological systems and in biotechnological applications. While the intrinsic stability of proteins is ultimately fixed by their amino acid composition and organization, the interactions between osmolytes and proteins together with their concentrations introduce an additional layer of complexity and in turn, a method of modulating protein stability. Here, we combined experimental measurements with molecular dynamics simulations and graph-theory-based analyses to predict the stabilizing/destabilizing effects of different kinds of osmolytes on proteins during heat-mediated denaturation.

Synchronized motion of interface residues for evaluating protein-RNA complex binding affinity: Application to aptamer-mediated inhibition of TDP-43 aggregates.

Investigating the binding between proteins and aptamers, such as peptides or RNA molecules, is of crucial importance both for understanding the molecular mechanisms that regulate cellular activities and for therapeutic applications in several pathologies. Here, a new computational procedure, employing mainly docking, clustering analysis, and molecular dynamics simulations, was designed to estimate the binding affinities between a protein and some RNA aptamers, through the investigation of the dynamical behavior of the predicted molecular complex. Using the state-of-the-art software catRAPID, we computationally designed a set of RNA aptamers interacting with the TAR DNA-binding protein 43 (TDP-43), a protein associated with several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS).

Dynamic Gene Expression Mitigates Mutational Escape in Lysis-Driven Bacteria Cancer Therapy.

Engineered bacteria have the potential to deliver therapeutic payloads directly to tumors, with synthetic biology enabling precise control over therapeutic release in space and time. However, it remains unclear how to optimize therapeutic bacteria for durable colonization and sustained payload release. Here, we characterize nonpathogenic expressing the bacterial toxin Perfringolysin O (PFO) and dynamic strategies that optimize therapeutic efficacy.

Lactoferrins in Their Interactions with Molecular Targets: A Structure-Based Overview.

Lactoferrins and lactoferrin-derived peptides display numerous functions linked to innate immunity in mammalians, spanning from antimicrobial to anti-inflammatory and immunomodulatory actions, and even demonstrate antitumor properties. To date, the proposed mechanisms for their biological actions are varied, although the molecular basis that governs lactoferrin interactions with molecular targets has been clarified only in a limited number of specific cases. However, key in silico methods have recently moved the topic to the fore, thus greatly expanding the possibilities of large-scale investigations on macromolecular interactions involving lactoferrins and their molecular targets.

Computational Approaches to Predict Protein-Protein Interactions in Crowded Cellular Environments.

Investigating protein-protein interactions is crucial for understanding cellular biological processes because proteins often function within molecular complexes rather than in isolation. While experimental and computational methods have provided valuable insights into these interactions, they often overlook a critical factor: the crowded cellular environment. This environment significantly impacts protein behavior, including structural stability, diffusion, and ultimately the nature of binding.