Abstract Motivation Protein–DNA interactions are essential for regulating many cellular processes, such as transcription, replication, recombination and translation. Amino acid mutations occurring in DNA-binding proteins have profound effects on protein–DNA binding linked with diseases. Hence, accurate fast predictions of the affinity understanding disease-causing mechanisms guiding plausible treatments. Results Here we report a new method Single Mutation free energy change Interaction...

Electrostatic potential, energies, and forces affect virtually any process in molecular biology, however, computing these quantities is a difficult task due to irregularly shaped macromolecules the presence of water. Here, we report new edition popular software package DelPhi along with describing its functionalities. The C++ object‐oriented supporting various levels multiprocessing memory distribution. It demonstrated that results significant improvement computational time. Furthermore, for...

2,3,5-Tris-(glutathion-S-yl)hydroquinone (TGHQ), a reactive metabolite of the nephrotoxicant hydroquinone, induces ROS-dependent activation MAPKs, followed by histone H3 phosphorylation and oncotic cell death in renal proximal tubule epithelial cells (LLC-PK(1)). Cell are attenuated pharmacological inhibition p38 MAPK or ERK1/2 pathways. Because TGHQ, but not epidermal growth factor (EGF), LLC-PK(1) cells, we hypothesized that there differences mechanisms which TGHQ EGF induce receptor...

Abstract Summary Electrostatic force is an essential component of the total acting between atoms and macromolecules. Therefore, accurate calculations electrostatic forces are crucial for revealing mechanisms many biological processes. We developed a DelPhiForce web server to calculate visualize at molecular level. enables modeling on individual atoms, residues, domains molecules, generates output that can be visualized by VMD software. Here we demonstrate usage various problems including...

Rationale: Corneal transplantation is an effective treatment to corneal blindness. However, the immune rejection imperils allograft survival. An interventional modality urgently needed inhibit and promote In our previous study, subconjunctival injections of bone marrow-derived mesenchymal stem cells (BM-MSCs) into a rat model extended survival for 2 d. this we sought generate IL-10-overexpressing BM-MSCs, aiming boost survival-promoting effects BM-MSCs on allografts explore molecular...

The ability to predict if a given mutation is disease-causing or not has enormous potential impact human health. Typically, these predictions are made by assessing the effects of on macromolecular stability and amino acid conservation. Here we report novel feature: electrostatic component force acting between kinesin motor domain tubulin. We demonstrate that changes in binding able discriminate non-disease-causing mutations found domains using receiver operating characteristic (ROC). Because...

The standard treatment of ions in the framework Poisson–Boltzmann equation relies on molecular surfaces, which are commonly constructed along with Stern layer. surface determines where can be present. In Gaussian-based smooth dielectric function DelPhi, boundaries between solute and solvent take place surface. Therefore, this invokes question how to model mobile water phase without a definite solute-solvent boundary. This article reports natural extension approach that treats via Boltzmann...

Typically, the ensemble average polar component of solvation energy (ΔGpolarsolv) a macromolecule is computed using molecular dynamics (MD) or Monte Carlo (MC) simulations to generate conformational and then single/rigid conformation calculation performed on each snapshot. The primary objective this work demonstrate that Poisson-Boltzmann (PB)-based approach Gaussian-based smooth dielectric function for macromolecular modeling previously developed by us (Li et al. J. Chem. Theory Comput....

11-Deoxy-16,16-dimethyl PGE(2) (DDM-PGE(2)) protects renal proximal tubule epithelial cells (LLC-PK(1)) against the toxicity induced by 2,3,5-tris(glutathion-S-yl)hydroquinone (TGHQ), a potent nephrotoxic and nephrocarcinogenic metabolite of hydroquinone. We have now determined ability DDM-PGE(2) to protect other toxicants report that only oncotic cell death, H(2)O(2), iodoacetamide, TGHQ, but not apoptotic death cisplatin, mercuric chloride, or tumor necrosis factor-alpha....

Conventional modeling techniques to model macromolecular solvation and its effect on binding in the framework of Poisson-Boltzmann based implicit solvent models make use a geometrically defined surface depict separation interior (low dielectric constant) from phase (high constant). Though this simplification saves time computational resources without significantly compromising accuracy free energy calculations, it bypasses some key physio-chemical properties solute-solvent interface, e.g....

A new feature of the popular software DelPhi is developed and reported, allowing for computing surface averaged electrostatic potential (SAEP) macromolecules. The user given option to specify distance from van der Waals where will be outputted. In conjunction with DelPhiPKa BION server, can adjust charges titratable groups according specific pH values, add explicit ions bound macromolecular surface. This approach applied a set four proteins "experimentally" delivered zeta (ζ)-potentials at...

Here we report a novel approach, the DelPhiForce Molecular Dynamics (DFMD) method, for steered molecular dynamics simulations to model receptor-ligand association. The main purpose of developing DFMD is simulate ligand's trajectory toward receptor and thus predict "entrance" binding pocket conformational changes associated with binding. We demonstrate that superior compared applying standard cut-offs, provides correct forces, allows modeling ligand approach at long distances guides spot, it...

Dry eye disease (DED) is often secondary to diabetes mellitus (DM).

Electrostatics play indispensable role in practically any process molecular biology. Indeed, at distances larger than several Angstroms all other forces are negligibly small and electrostatic force dominates. However, modeling electrostatics biology is a complicated task due to presence of water phase, mobile ions irregularly shaped inhomogeneous biological macromolecules. A particular approach calculating such systems apply Poisson-Boltzmann equation (PBE). Here we provide tutorial for the...

One of the anthrax receptors, tumor endothelial marker 8 (TEM8), is reported to be a potential anticancer target due its over‐expression during angiogenesis. To extend our BioLayer Interferometry study in PA‐TEM8 binding, we present computational approach reveal role an integral metal ion on receptor structure and binding thermodynamics. We estimated interaction energy between PA TEM8 using computer simulation. Consistent with experimental study, results indicate contributes significantly...

To observe the decentration and tilt of implantable collamer lens (ICL) as well possible visual effects postimplantation in primary iridociliary cysts.The present investigation was a retrospective cohort study. All 48 patients (91 eyes) who underwent ICL surgery at Center Refraction Surgery Tianjin Medical University Eye Hospital between July 2018 May 2020 were split into two groups based on absence or presence cysts established by ultrasonic biological microscopy (UBM) examination....

Both enterprise and national firewalls filter network connections. For data forensics botnet removal applications, it is important to establish the information source. In this paper, we describe a transport layer which allows client transfer encrypted that provides no discernible regarding We use domain generation algorithm (DGA) encode AES into names current tools are unable reliably differentiate from valid names. The registered using (free) dynamic DNS services. transmission format not...

Prostaglandins (PGs) act locally to maintain cellular homeostasis and stimulate stress response signaling pathways. These effects are diverse tissue-dependent. PGE2, the synthetic analogue, 11-deoxy,16,16-dimethyl PGE2 (DDM-PGE2), protect renal proximal tubular epithelial (LLC-PK1) cells against injury induced by potent nephrotoxic nephrocarcinogenic metabolite of hydroquinone, 2,3,5-tris-(glutathion-S-yl)hydroquinone. Although this cytoprotective (in LLC-PK1 cells) is mediated through a...

Integrins are cellular adhesion proteins located on cell surface. They known to have open and closed conformations that correspond high low binding affinity ligands, respectively. Integrin [Formula: see text]2 binds the ligands via ligand domain, text]2-I which also has conformations. Experimentally, conformation change is shown be triggered by pulling C-terminal away from site, but how signal propagates distant site unknown. To explain mechanisms of change, we built models domain in free...