Search results for "PROTEIN-PROTEIN INTERACTION"

Targeting SARS-CoV-2 RBD Interface: a Supervised Computational Data-Driven Approach to Identify Potential Modulators

2020

Coronavirus disease 2019 (COVID-19) has spread out as a pandemic threat affecting over 2 million people. The infectious process initiates via binding of SARS-CoV-2 Spike (S) glycoprotein to host angiotensin-converting enzyme 2 (ACE2). The interaction is mediated by the receptor-binding domain (RBD) of S glycoprotein, promoting host receptor recognition and binding to ACE2 peptidase domain (PD), thus representing a promising target for therapeutic intervention. Herein, we present a computational study aimed at identifying small molecules potentially able to target RBD. Although targeting PPI remains a challenge in drug discovery, our investigation highlights that interaction between SARS-CoV…

Changes in the proteome of sea urchin Paracentrotus lividus coelomocytes in response to LPS injection into the body cavity.

2020

Background The immune system of echinoderm sea urchins is characterised by a high degree of complexity that is not completely understood. The Mediterranean sea urchin Paracentrotus lividus coelomocytes mediate immune responses through phagocytosis, encapsulation of non-self particles, and production of diffusible factors including antimicrobial molecules. Details of these processes, and molecular pathways driving these mechanisms, are still to be fully elucidated. Principal findings In the present study we treated the sea urchin P. lividus with the bacterial lipopolysaccharide (LPS) and collected coelomocytes at different time-points (1, 3, 6 and 24 hours). We have shown, using label-free q…

PREDICTION OF THERMODYNAMIC INSTABILITIES OF PROTEIN SOLUTIONS FROM SIMPLE PROTEIN-PROTEIN INTERACTIONS

2013

Statistical thermodynamics of protein solutions is often studied in terms of simple, microscopic models of particles interacting via pairwise potentials. Such modelling can reproduce the short range structure of protein solutions at equilibrium and predict thermodynamics instabilities of these systems. We introduce a square well model of effective protein-protein interaction that embeds the solvent's action. We modify an existing model [45] by considering a well depth having an explicit dependence on temperature, i.e. an explicit free energy character, thus encompassing the statistically relevant configurations of solvent molecules around proteins. We choose protein solutions exhibiting dem…

Identification of Key miRNAs in Regulation of PPI Networks

2020

In this paper, we explore the interaction between miRNA and deregulated proteins in some pathologies. Assuming that miRNA can influence mRNA and consequently the proteins regulation, we explore this connection by using an interaction matrix derived from miRNA-target data and PPI network interactions. From this interaction matrix and the set of deregulated proteins, we search for the miRNA subset that influences the deregulated proteins with a minimum impact on the not deregulated ones. This regulation problem can be formulated as a complex optimization problem. In this paper, we have tried to solve it by using the Genetic Algorithm Heuristic. As the main result, we have found a set of miRNA…

Algorithms for Graph and Network Analysis: Graph Alignment

2019

In this article we discuss the problem of graph alignment, which has been longly referred to for the purpose of analyzing and comparing biological networks. In particular, we describe different facets of graph alignment, according to the number of input networks, the fixed output objective, the possible heterogeneity of input data. Accordingly, we will discuss pairwise and multiple alignment, global and local alignment, etc. Moreover, we provide a comprehensive overview of the algorithms and techniques proposed in the literature to solve each of the specific considered types of graph alignment. In order to make the material presented here complete and useful to guide the reader in the use o…

NMR structure of a non-conjugatable, ADP-ribosylation associated, ubiquitin-like domain from Tetrahymena thermophila polyubiquitin locus.

2019

Abstract Background Ubiquitin-like domains (UbLs), in addition to being post-translationally conjugated to the target through the E1-E2-E3 enzymatic cascade, can be translated as a part of the protein they ought to regulate. As integral UbLs coexist with the rest of the protein, their structural properties can differ from canonical ubiquitin, depending on the protein context and how they interact with it. In this work, we investigate T.th-ubl5, a UbL present in a polyubiquitin locus of Tetrahymena thermophila, which is integral to an ADP-ribosyl transferase protein. Only one other co-occurrence of these two domains within the same protein has been reported. Methods NMR, multiple sequence al…

Structure-function analysis of peroxisomal ATP-binding cassette transporters using chimeric dimers

2014

Background: Peroxisomal ABC transporters are predicted to function as homodimers in mammals. [br/] Results: ABCD1 interacts with ABCD2. Chimeric proteins mimicking full-length dimers represent novel tools for functional study. Artificial homodimers and heterodimers are functional. [br/] Conclusion: Interchangeability between ABCD1 and ABCD2 is confirmed, but PUFA transport depends on ABCD2. [br/] Significance: For the first time, heterodimers in mammals are proven to be functional.[br/] ABCD1 and ABCD2 are two closely related ATP-binding cassette half-transporters predicted to homodimerize and form peroxisomal importers for fatty acyl-CoAs. Available evidence has shown that ABCD1 and ABCD2 …

Synthesis and biological evaluation of some new 2-phenylpropiolamidobenzamides as potential antagonists of the HDM2-p53 protein-protein interactions

2009

Restricted Neighborhood search clustering revisited: an evolutionary computation perspective

2013

The Interaction Mechanism of Intrinsically Disordered PP2A Inhibitor Proteins ARPP-16 and ARPP-19 With PP2A

2021

Protein phosphatase 2A (PP2A) activity is critical for maintaining normal physiological cellular functions. PP2A is inhibited by endogenous inhibitor proteins in several pathological conditions including cancer. A PP2A inhibitor protein, ARPP-19, has recently been connected to several human cancer types. Accordingly, the knowledge about ARPP-19—PP2A inhibition mechanism is crucial for the understanding the disease development and the therapeutic targeting of ARPP-19—PP2A. Here, we show the first structural characterization of ARPP-19, and its splice variant ARPP-16 using NMR spectroscopy, and SAXS. The results reveal that both ARPP proteins are intrinsically disordered but contain transient…