Encoding the space of protein-protein binding interfaces by artificial intelligence.

The physical interactions between proteins are largely determined by the structural properties at their binding interfaces. It was found that the binding interfaces in distinctive protein complexes are highly similar. The structural properties underlying different binding interfaces could be further captured by artificial intelligence.

Withdrawal notice to "Structural and functional characterization for interaction of silver nanoparticles with ergostrol in Trichoderma harzianum" [Microb. Pathog. 125 (2018) 318-324].

This article has been withdrawn at the request of the editor and publisher. The publisher regrets that an error occurred which led to the premature publication of this paper. This error bears no reflection on the article or its authors.

Computational analyses of the interactome between TNF and TNFR superfamilies.

Proteins in the tumor necrosis factor (TNF) superfamily (TNFSF) regulate diverse cellular processes by interacting with their receptors in the TNF receptor (TNFR) superfamily (TNFRSF). Ligands and receptors in these two superfamilies form a complicated network of interactions, in which the same ligand can bind to different receptors and the same receptor can be shared by different ligands. In order to study these interactions on a systematic level, a TNFSF-TNFRSF interactome was constructed in this study by searching the database which consists of both experimentally measured and computationally predicted protein-protein interactions (PPIs).

Understanding the functional role of membrane confinements in TNF-mediated signaling by multiscale simulations.

The interaction between TNFα and TNFR1 is essential in maintaining tissue development and immune responses. While TNFR1 is a cell surface receptor, TNFα exists in both soluble and membrane-bound forms. Interestingly, it was found that the activation of TNFR1-mediated signaling pathways is preferentially through the soluble form of TNFα, which can also induce the clustering of TNFR1 on plasma membrane of living cells.

EXCESP: A Structure-Based Online Database for Extracellular Interactome of Cell Surface Proteins in Humans.

The interactions between ectodomains of cell surface proteins are vital players in many important cellular processes, such as regulating immune responses, coordinating cell differentiation, and shaping neural plasticity. However, while the construction of a large-scale protein interactome has been greatly facilitated by the development of high-throughput experimental techniques, little progress has been made to support the discovery of extracellular interactome for cell surface proteins. Harnessed by the recent advances in computational modeling of protein-protein interactions, here we present a structure-based online database for the extracellular interactome of cell surface proteins in humans, called EXCESP.

A structural-based machine learning method to classify binding affinities between TCR and peptide-MHC complexes.

The activation of T cells is triggered by the interactions of T cell receptors (TCRs) with their epitopes, which are peptides presented by major histocompatibility complex (MHC) on the surfaces of antigen presenting cells (APC). While each TCR can only recognize a specific subset from a large repertoire of peptide-MHC (pMHC) complexes, it is very often that peptides in this subset share little sequence similarity. This is known as the specificity and cross-reactivity of T cells, respectively.

Classification of protein-protein association rates based on biophysical informatics.

Background: Proteins form various complexes to carry out their versatile functions in cells. The dynamic properties of protein complex formation are mainly characterized by the association rates which measures how fast these complexes can be formed. It was experimentally observed that the association rates span an extremely wide range with over ten orders of magnitudes.

Coarse-grained simulations of phase separation driven by DNA and its sensor protein cGAS.

The enzyme cGAS functions as a sensor that recognizes the cytosolic DNA from foreign pathogen. The activation of the protein triggers the transcription of inflammatory genes, leading into the establishment of an antipathogen state. An interesting new discovery is that the detection of DNA by cGAS induced the formation of liquid-like droplets.

Bioengineering of Genetically Encoded Gene Promoter Repressed by the Flavonoid Apigenin for Constructing Intracellular Sensor for Molecular Events.

In recent years, Synthetic Biology has emerged as a new discipline where functions that were traditionally performed by electronic devices are replaced by "cellular devices"; genetically encoded circuits constructed of DNA that are built from biological parts (aka bio-parts). The cellular devices can be used for sensing and responding to natural and artificial signals. However, a major challenge in the field is that the crosstalk between many cellular signaling pathways use the same signaling endogenous molecules that can result in undesired activation.

Mechanistic dissection of spatial organization in NF-κB signaling pathways by hybrid simulations.

The nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is one of the most important transcription factors involved in the regulation of inflammatory signaling pathways. Inappropriate activation of these pathways has been linked to autoimmunity and cancers. Emerging experimental evidences have been showing the existence of elaborate spatial organizations for various molecular components in the pathways.

A multiscale study on the mechanisms of spatial organization in ligand-receptor interactions on cell surfaces.

The binding of cell surface receptors with extracellular ligands triggers distinctive signaling pathways, leading into the corresponding phenotypic variation of cells. It has been found that in many systems, these ligand-receptor complexes can further oligomerize into higher-order structures. This ligand-induced oligomerization of receptors on cell surfaces plays an important role in regulating the functions of cell signaling.

A computational study of co-inhibitory immune complex assembly at the interface between T cells and antigen presenting cells.

The activation and differentiation of T-cells are mainly directly by their co-regulatory receptors. T lymphocyte-associated protein-4 (CTLA-4) and programed cell death-1 (PD-1) are two of the most important co-regulatory receptors. Binding of PD-1 and CTLA-4 with their corresponding ligands programed cell death-ligand 1 (PD-L1) and B7 on the antigen presenting cells (APC) activates two central co-inhibitory signaling pathways to suppress T cell functions.

Understanding the impacts of cellular environments on ligand binding of membrane receptors by computational simulations.

Binding of cell surface receptors with their extracellular ligands initiates various intracellular signaling pathways. However, our understanding of the cellular functions of these receptors is very limited due to the fact that in vivo binding between ligands and receptors has only been successfully measured in a very small number of cases. In living cells, receptors are anchored on surfaces of the plasma membrane, which undergoes thermal undulations.

Understand the Functions of Scaffold Proteins in Cell Signaling by a Mesoscopic Simulation Method.

Scaffold proteins are central players in regulating the spatial-temporal organization of many important signaling pathways in cells. They offer physical platforms to downstream signaling proteins so that their transient interactions in a crowded and heterogeneous environment of cytosol can be greatly facilitated. However, most scaffold proteins tend to simultaneously bind more than one signaling molecule, which leads to the spatial assembly of multimeric protein complexes.

Using Coarse-Grained Simulations to Characterize the Mechanisms of Protein-Protein Association.

The formation of functionally versatile protein complexes underlies almost every biological process. The estimation of how fast these complexes can be formed has broad implications for unravelling the mechanism of biomolecular recognition. This kinetic property is traditionally quantified by association rates, which can be measured through various experimental techniques.

Understanding the Impacts of Conformational Dynamics on the Regulation of Protein-Protein Association by a Multiscale Simulation Method.

Complexes formed among diverse proteins carry out versatile functions in nearly all physiological processes. Association rates which measure how fast proteins form various complexes are of fundamental importance to characterize their functions. The association rates are not only determined by the energetic features at binding interfaces of a protein complex but also influenced by the intrinsic conformational dynamics of each protein in the complex.

An analysis of deleterious single nucleotide polymorphisms and molecular dynamics simulation of disease linked mutations in genes responsible for neurodegenerative disorder.

Mutation in two genes deglycase gene (DJ-1) and retromer complex component gene (VPS35) are linked with neurodegenerative disorder such as Parkinson's disease, Huntington's disease, and Alzheimer's disease. DJ-1 gene located at 1p36 chromosomal position and involved in PD pathogenesis through many pathways including mitochondrial dysfunction and oxidative injury. VPS35 gene located at 16q13-q21 chromosomal position and the two pathways, the Wnt signaling pathway, and retromer-mediated DMT1 missorting are proposed for basis of VPS35 related PD.

Biochemical regulation and structural analysis of copper-transporting ATPase in a human hepatoma cell line for Wilson disease.

Hepatic copper levels differ among patients with Wilson disease (WD) and normal individuals depending on the dietary intake, copper bioavailability, and genetic factors. Copper chloride (CuCl ) caused dose-dependent reduction in cell viability of human teratocarcinoma (HepG2) cell line, measured using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Cells were exposed to different concentrations of CuCl in log doses and maximum cell viability reduction was recorded at 15 µg/mL.

Molecular dynamics simulation analysis of conessine against multi drug resistant Serratia marcescens.

Ornithine decarboxylase (ODC) is an immediate precursor of polyamine biosynthesis in Serratia marcescens and a potential target for inhibition of its growth. We predicted the 3D structural conformation of ODC enzyme and validated it using MDS in our previous study. In this current study, the potential inhibitors of ODC were obtained by virtual screening of potential inhibitors from ZINC database and studied in depth for their different binding pose.

WITHDRAWN: Structural and functional characterization for interaction of silver nanoparticles with ergostrol in Trichoderma harzianum.

This article has been withdrawn: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy).

Overcoming antibiotic resistance: Is siderophore Trojan horse conjugation an answer to evolving resistance in microbial pathogens?

Comparative study of siderophore biosynthesis pathway in pathogens provides potential targets for antibiotics and host drug delivery as a part of computationally feasible microbial therapy. Iron acquisition using siderophore models is an essential and well established model in all microorganisms and microbial infections a known to cause great havoc to both plant and animal. Rapid development of antibiotic resistance in bacterial as well as fungal pathogens has drawn us at a verge where one has to get rid of the traditional way of obstructing pathogen using single or multiple antibiotic/chemical inhibitors or drugs.

Nicotinic acetylcholine receptor alpha 1(nAChRα1) subunit peptides as potential antiviral agents against rabies virus.

Rabies virus (RABV) is neurotropic and infects all warm-blooded animals. The binding of the virus with host cell receptor components is critical for infection. The present study reports the interaction of nicotinic acetylcholine receptor alpha 1 (nAChRα1) peptides with the rabies virus glycoprotein (RABVG) to design potential anti-rabies agents.