PyPCN: protein contact networks in PyMOL.

Motivation: Protein contact networks (PCNs) represent the 3D structure of a protein using network formalism. Inter-residue contacts are described as binary adjacency matrices, which are derived from the graph representation of residues (as α-carbons, β-carbons or centroids) and Euclidean distances according to defined thresholds. Functional characterization algorithms are computed on binary adjacency matrices to unveil allosteric, dynamic, and interaction mechanisms in proteins.

Head or tail? A molecular dynamics approach to the complex structure of TNF-associated factor TRAF2.

Tumor necrosis factor receptor-associated factor proteins (TRAFs) are trimeric proteins that play a fundamental role in signaling, acting as intermediaries between the tumor necrosis factor (TNF) receptors and the proteins that transmit the downstream signal. The monomeric subunits of all the TRAF family members share a common tridimensional structure: a C-terminal globular domain and a long coiled-coil tail characterizing the N-terminal section. In this study, the dependence of the TRAF2 dynamics on the length of its tail was analyzed .

Computational analysis of the sequence-structure relation in SARS-CoV-2 spike protein using protein contact networks.

The structure of proteins impacts directly on the function they perform. Mutations in the primary sequence can provoke structural changes with consequent modification of functional properties. SARS-CoV-2 proteins have been extensively studied during the pandemic.

A Statistical Journey through the Topological Determinants of the β2 Adrenergic Receptor Dynamics.

Activation of G-protein-coupled receptors (GPCRs) is mediated by molecular switches throughout the transmembrane region of the receptor. In this work, we continued along the path of a previous computational study wherein energy transport in the β2 Adrenergic Receptor (β2-AR) was examined and allosteric switches were identified in the molecular structure through the reorganization of energy transport networks during activation. In this work, we further investigated the allosteric properties of β2-AR, using Protein Contact Networks (PCNs).

PCN-Miner: an open-source extensible tool for the analysis of Protein Contact Networks.

Motivation: Protein Contact Network (PCN) is a powerful method for analysing the structure and function of proteins, with a specific focus on disclosing the molecular features of allosteric regulation through the discovery of modular substructures. The importance of PCN analysis has been shown in many contexts, such as the analysis of SARS-CoV-2 Spike protein and its complexes with the Angiotensin Converting Enzyme 2 (ACE2) human receptors. Even if there exist many software tools implementing such methods, there is a growing need for the introduction of tools integrating existing approaches.

Biophysical Insight into the SARS-CoV2 Spike-ACE2 Interaction and Its Modulation by Hepcidin through a Multifaceted Computational Approach.

At the center of the SARS-CoV2 infection, the spike protein and its interaction with the human receptor ACE2 play a central role in the molecular machinery of SARS-CoV2 infection of human cells. Vaccine therapies are a valuable barrier to the worst effects of the virus and to its diffusion, but the need of purposed drugs is emerging as a core target of the fight against COVID19. In this respect, the repurposing of drugs has already led to discovery of drugs thought to reduce the effects of the cytokine storm, but still a drug targeting the spike protein, in the infection stage, is missing.

The Odd Faces of Oligomers: The Case of TRAF2-C, A Trimeric C-Terminal Domain of TNF Receptor-Associated Factor.

TNF Receptor Associated Factor 2 (TRAF2) is a trimeric protein that belongs to the TNF receptor associated factor family (TRAFs). The TRAF2 oligomeric state is crucial for receptor binding and for its interaction with other proteins involved in the TNFR signaling. The monomer-trimer equilibrium of a C- terminal domain truncated form of TRAF2 (TRAF2-C), plays also a relevant role in binding the membrane, causing inward vesiculation.

Polymorphism on human aromatase affects protein dynamics and substrate binding: spectroscopic evidence.

Human aromatase is a member of the cytochrome P450 superfamily, involved in steroid hormones biosynthesis. In particular, it converts androgen into estrogens being therefore responsible for the correct sex steroids balance. Due to its capacity in producing estrogens it has also been considered as a promising target for breast cancer therapy.

Dynamic Network Modeling of Allosteric Interactions and Communication Pathways in the SARS-CoV-2 Spike Trimer Mutants: Differential Modulation of Conformational Landscapes and Signal Transmission via Cascades of Regulatory Switches.

The rapidly growing body of structural and biochemical studies of the SARS-CoV-2 spike glycoprotein has revealed a variety of distinct functional states with radically different arrangements of the receptor-binding domain, highlighting a remarkable function-driven conformational plasticity and adaptability of the spike proteins. In this study, we examined molecular mechanisms underlying conformational and dynamic changes in the SARS-CoV-2 spike mutant trimers through the lens of dynamic analysis of allosteric interaction networks and atomistic modeling of signal transmission. Using an integrated approach that combined coarse-grained molecular simulations, protein stability analysis, and perturbation-based modeling of residue interaction networks, we examined how mutations in the regulatory regions of the SARS-CoV-2 spike protein can differentially affect dynamics and allosteric signaling in distinct functional states.

Protein Assembly: Defining the Strength of Protein-Protein Interactions Coupling the Theory with Experiments.

In this paper we report a procedure to analyze protein homodimer interfaces.We approached the problem by means of a topological methodology. In particular, we analyzed the subunits interface of about 50 homodimers and we have defined a few parameters that allow to organize these proteins in six different classes.

Disclosing Allostery Through Protein Contact Networks.

Proteins are located in the twilight zone between chemistry and biology, where a peculiar kind of complexity starts. Proteins are the smallest 'devices' showing a sensible adaptation to their environment by the production of appropriate behavior when facing a specific stimulus. This fact qualifies (from the 'effector' side) proteins as nanomachines working as catalysts, motors, or switches.

Fishery Wastes as a Yet Undiscovered Treasure from the Sea: Biomolecules Sources, Extraction Methods and Valorization.

The search for new biological sources of commercial value is a major goal for the sustainable management of natural resources. The huge amount of fishery by-catch or processing by-products continuously produced needs to be managed to avoid environmental problems and keep resource sustainability. Fishery by-products can represent an interesting source of high added value bioactive compounds, such as proteins, carbohydrates, collagen, polyunsaturated fatty acids, chitin, polyphenolic constituents, carotenoids, vitamins, alkaloids, tocopherols, tocotrienols, toxins; nevertheless, their biotechnological potential is still largely underutilized.

Cardiovascular Active Peptides of Marine Origin with ACE Inhibitory Activities: Potential Role as Anti-Hypertensive Drugs and in Prevention of SARS-CoV-2 Infection.

Growing interest in hypertension-one of the main factors characterizing the cardiometabolic syndrome (CMS)-and anti-hypertensive drugs raised from the emergence of a new coronavirus, SARS-CoV-2, responsible for the COVID19 pandemic. The virus SARS-CoV-2 employs the Angiotensin-converting enzyme 2 (ACE2), a component of the RAAS (Renin-Angiotensin-Aldosterone System) system, as a receptor for entry into the cells. Several classes of synthetic drugs are available for hypertension, rarely associated with severe or mild adverse effects.

Effects of protein-protein interface disruptors at the ligand of the glucocorticoid-induced tumor necrosis factor receptor-related gene (GITR).

The tumor necrosis factor (TNF) superfamily (TNFSF) includes about thirty structurally related receptors (TNFSFRs) and about twenty protein ligands that bind to one or more of these receptors. Receptors of the tumor necrosis factor (TNF) superfamily (TNFSFRs) are pharmacological targets for treatment of inflammatory and autoimmune diseases. Currently, drugs targeting TNFSFR signaling are biological drugs (monoclonal antibodies, decoy receptors) aimed at binding and sequestering TNFSFR ligands.

The Discovery of a Putative Allosteric Site in the SARS-CoV-2 Spike Protein Using an Integrated Structural/Dynamic Approach.

SARS-CoV-2 has caused the largest pandemic of the twenty-first century (COVID-19), threatening the life and economy of all countries in the world. The identification of novel therapies and vaccines that can mitigate or control this global health threat is among the most important challenges facing biomedical sciences. To construct a long-term strategy to fight both SARS-CoV-2 and other possible future threats from coronaviruses, it is critical to understand the molecular mechanisms underlying the virus action.

Novel indole derivatives targeting HuR-mRNA complex to counteract high glucose damage in retinal endothelial cells.

The ELAVL1 (or human antigen R - HuR) RNA binding protein stabilizes the mRNA, with an AU-rich element, of several genes such as growth factors (i.e. VEGF) and inflammatory cytokines (i.

Non-symmetrical structural behavior of a symmetric protein: the case of homo-trimeric TRAF2 (tumor necrosis factor-receptor associated factor 2).

The oligomeric state of TRAF2 (tumor necrosis factor-receptor associated factor 2), a TNF (tumor necrosis factor) receptor-associated factor, is crucial for membrane binding and probably plays a fundamental role in regulating the protein function in vivo. In this study we have combined molecular dynamics with the protein contact network approach to characterize the interaction of the three identical subunits of TRAF2. The average structure obtained after a 225 ns simulation reveals that two clusters of different size are formed, one of which includes almost completely two subunits, while the third monomer appears to be more independent.

Auxin minimum triggers the developmental switch from cell division to cell differentiation in the root.

In multicellular organisms, a stringent control of the transition between cell division and differentiation is crucial for correct tissue and organ development. In the root, the boundary between dividing and differentiating cells is positioned by the antagonistic interaction of the hormones auxin and cytokinin. Cytokinin affects polar auxin transport, but how this impacts the positional information required to establish this tissue boundary, is still unknown.

P2X7 receptor antagonism: Implications in diabetic retinopathy.

Diabetic retinopathy (DR) is the most frequent complication of diabetes and one of leading causes of blindness worldwide. Early phases of DR are characterized by retinal pericyte loss mainly related to concurrent inflammatory process. Recently, an important link between P2X7 receptor (P2X7R) and inflammation has been demonstrated indicating this receptor as potential pharmacological target in DR.

Comparative Study of Elastic Network Model and Protein Contact Network for Protein Complexes: The Hemoglobin Case.

The overall topology and interfacial interactions play key roles in understanding structural and functional principles of protein complexes. Elastic Network Model (ENM) and Protein Contact Network (PCN) are two widely used methods for high throughput investigation of structures and interactions within protein complexes. In this work, the comparative analysis of ENM and PCN relative to hemoglobin (Hb) was taken as case study.

GH32 family activity: a topological approach through protein contact networks.

The application of Protein Contact Networks methodology allowed to highlight a novel response of border region between the two domains to substrate binding. Glycoside hydrolases (GH) are enzymes that mainly hydrolyze the glycosidic bond between two carbohydrates or a carbohydrate and a non-carbohydrate moiety. These enzymes are involved in many fundamental and diverse biological processes in plants.