A Sustainable Approach to Valuable Polyphenol and Iridoid Antioxidants from Medicinal Plant By-Products.

Supply chain waste gives rise to significant challenges in terms of disposal, making upcycling a promising and sustainable alternative for the recovery of bioactive compounds from by-products. Lignocellulosic by-products like STF231, which are derived from the medicinal plant extract industry, offer valuable compounds such as polyphenols and iridoids that can be recovered through upcycling. In an unprecedented study, we explored and compared conventional hydroethanolic extraction, ultrasound hydroethanolic extraction, and natural deep eutectic solvents-ultrasound extraction methods on STF231 to obtain extracts with antioxidant activity.

2G-lactic acid from olive oil supply chain waste: olive leaves upcycling via Lactobacillus casei fermentation.

The transition towards a sustainable model, particularly the circular economy, emphasizes the importance of redefining waste as a valuable resource, paving the way for innovative upcycling strategies. The olive oil industry, with its significant output of agricultural waste, offers a promising avenue for high-value biomass conversion into useful products through microbial processes. This study focuses on exploring new, high-value applications for olive leaves waste, utilizing a biotechnological approach with Lactobacillus casei for the production of second-generation lactic acid.

Decrypting Allostery in Membrane-Bound K-Ras4B Using Complementary Approaches Based on Unbiased Molecular Dynamics Simulations.

Protein functions are dynamically regulated by allostery, which enables conformational communication even between faraway residues, and expresses itself in many forms, akin to different "languages": allosteric control pathways predominating in an unperturbed protein are often unintuitively reshaped whenever biochemical perturbations arise (, mutations). To accurately model allostery, unbiased molecular dynamics (MD) simulations require integration with a reliable method able to, , detect incipient allosteric changes or likely perturbation pathways; this is because allostery can operate at longer time scales than those accessible by plain MD. Such methods are typically applied singularly, but we here argue their joint application─as a "multilingual" approach─could work significantly better.

Conformational Behavior of SARS-Cov-2 Spike Protein Variants: Evolutionary Jumps in Sequence Reverberate in Structural Dynamic Differences.

SARS-CoV-2 has evolved rapidly in the first 3 years of pandemic diffusion. The initial evolution of the virus appeared to proceed through big jumps in sequence changes rather than through the stepwise accumulation of point mutations on already established variants. Here, we examine whether this nonlinear mutational process reverberates in variations of the conformational dynamics of the SARS-CoV-2 Spike protein (S-protein), the first point of contact between the virus and the human host.

Protein Allostery and Ligand Design: Computational Design Meets Experiments to Discover Novel Chemical Probes.

Herein we examine the determinants of the allosteric inhibition of the mitochondrial chaperone TRAP1 by a small molecule ligand. The knowledge generated is harnessed into the design of novel derivatives with interesting biological properties. TRAP1 is a member of the Hsp90 family of proteins, which work through sequential steps of ATP processing coupled to client-protein remodeling.

Machine Learning Prediction of Allosteric Drug Activity from Molecular Dynamics.

Allosteric drugs have been attracting increasing interest over the past few years. In this context, it is common practice to use high-throughput screening for the discovery of non-natural allosteric drugs. While the discovery stage is supported by a growing amount of biological information and increasing computing power, major challenges still remain in selecting allosteric ligands and predicting their effect on the target protein's function.

The Answer Lies in the Energy: How Simple Atomistic Molecular Dynamics Simulations May Hold the Key to Epitope Prediction on the Fully Glycosylated SARS-CoV-2 Spike Protein.

SARS-CoV-2 is a health threat with dire socioeconomical consequences. As the crucial mediator of infection, the viral glycosylated spike protein (S) has attracted the most attention and is at the center of efforts to develop therapeutics and diagnostics. Herein, we use an original decomposition approach to identify energetically uncoupled substructures as antibody binding sites on the fully glycosylated S.

The Subtle Trade-Off between Evolutionary and Energetic Constraints in Protein-Protein Interactions.

Life machinery, although overwhelmingly complex, is rooted on a rather limited number of molecular processes. One of the most important is protein-protein interaction. Metabolic regulation, protein folding control, and cellular motility are examples of processes based on the fine-tuned interaction of several protein partners.

Formulation and Characterization of Native and Crosslinked Hyaluronic Acid Microspheres for Dermal Delivery of Sodium Ascorbyl Phosphate: A Comparative Study.

The present work evaluates for the first time the use of urea-crosslinked hyaluronic acid (HA-CL), a novel derivative of native hyaluronic acid (HA), to produce microspheres (MS) by emulsification-solvent evaporation, for dermal delivery of sodium ascorbyl phosphate (SAP). As the term of comparison, HA MS were prepared. A pre-formulation study-investigation of the effects of polymers solutions properties (pH, viscosity) and working conditions-led to the - production of optimized HA-CL MS and HA-CL-SAP MS with: almost unimodal size distributions; mean diameter of 13.

The Interplay between Structural Stability and Plasticity Determines Mutation Profiles and Chaperone Dependence in Protein Kinases.

We present a novel comparative analysis of representative protein kinases to characterize the main dynamic and energetic determinants of functional regulation shared among different families. The relationships between stability and plasticity are also used to rationalize kinase tendencies to interact with the molecular chaperone Hsp90. These questions are tackled through newly developed molecular-dynamics-based methods of analysis of internal energy and dynamics applied to a total of 37 different systems, which represent wild-type and mutated proteins, including active and inactive states.

How likely are oscillations in a genetic feedback loop with delay?

Some genetic control networks display temporal oscillations as a result of delays in their homeostatic control. A relevant question about these systems is whether the oscillating regime is a rare feature, or it corresponds to a sizeable volume of the space of parameters. The answer is not trivial mainly due to the large number of parameters controlling the rate equations which describe the network.

SAGE: A Fast Computational Tool for Linear Epitope Grafting onto a Foreign Protein Scaffold.

Computational design is becoming a driving force of structural vaccinology, whereby protein antigens are engineered to generate new biomolecules with optimized immunological properties. In particular, the design of new proteins that contain multiple, different epitopes can potentially provide novel highly efficient vaccine candidates. In this context, epitope grafting, which entails the transplantation of an antibody recognition motif from one protein onto a different protein scaffold (possibly containing other immunoreactive sequences) holds great promise for the realization of superantigens.