<em>In silico</em> identification of RBD subdomain of spike protein from Pro<sup>322</sup>-Thr<sup>581</sup> for applications in vaccine development against SARS-CoV2

6 days 6 hours ago
The three-dimensional hybrid structures of coronavirus spike proteins including the C-terminal sequence and receptor binding motif (RBM) was remodeled and energy minimized. Further, protein-protein docking show that Receptor Binding Domain (RBD) of SARS-CoV 2 Lys^(457)-Pro^(490) bind on the surface of ACE2 receptor near N-terminal helices to form host-pathogen attachment. In this binding interface, SARS-CoV 2 shows a tight network of hydrogen bonds than other spike proteins from BtRsRaTG13-CoV,...
Nataraj S Pagadala

Modeling Microtubule Counterion Distributions and Conductivity Using the Poisson-Boltzmann Equation

1 month ago
Microtubules are highly negatively charged proteins which have been shown to behave as bio-nanowires capable of conducting ionic currents. The electrical characteristics of microtubules are highly complicated and have been the subject of previous work; however, the impact of the ionic concentration of the buffer solution on microtubule electrical properties has often been overlooked. In this work we use the non-linear Poisson Boltzmann equation, modified to account for a variable permittivity...
Boden B Eakins

The Uniqueness of Albumin as a Carrier in Nanodrug Delivery

1 month 2 weeks ago
Albumin is an appealing carrier in nanomedicine because of its unique features. First, it is the most abundant protein in plasma, endowing high biocompatibility, biodegradability, nonimmunogenicity, and safety for its clinical application. Second, albumin chemical structure and conformation allows interaction with many different drugs, potentially protecting them from elimination and metabolism in vivo, thus improving their pharmacokinetic properties. Finally, albumin can interact with receptors...
Alessandra Spada

Insights into the interaction dynamics between volatile anesthetics and tubulin through computational molecular modelling

2 months ago
General anesthetics, able to reversibly suppress all conscious brain activity, have baffled medical science for decades, and little is known about their exact molecular mechanism of action. Given the recent scientific interest in the exploration of microtubules as putative functional targets of anesthetics, and the involvement thereof in neurodegenerative disorders, the present work focuses on the investigation of the interaction between human tubulin and four volatile anesthetics: ethylene,...
Eric A Zizzi

First Search for Dyons with the Full MoEDAL Trapping Detector in 13 TeV pp Collisions

2 months 1 week ago
The MoEDAL trapping detector consists of approximately 800 kg of aluminum volumes. It was exposed during run 2 of the LHC program to 6.46 fb^{-1} of 13 TeV proton-proton collisions at the LHCb interaction point. Evidence for dyons (particles with electric and magnetic charge) captured in the trapping detector was sought by passing the aluminum volumes comprising the detector through a superconducting quantum interference device (SQUID) magnetometer. The presence of a trapped dyon would be...
B Acharya

An insight into the anticancer potential of carbamates and thiocarbamates of 10-demethoxy-10-methylaminocolchicine

2 months 3 weeks ago
Colchicine shows very high antimitotic activity, therefore, it is used as a lead compound for generation of new anticancer agents. In the hope of developing novel, useful drugs with more favourable pharmacological profiles, a series of doubly modified colchicine derivatives has been designed, synthesized and characterized. These novel carbamate or thiocarbamate derivatives of 10-demethoxy-10-methylaminocolchicine have been tested for their antiproliferative activity against four human cancer...
Julia Krzywik

JAK inhibitors in immune-mediated rheumatic diseases: From a molecular perspective to clinical studies

3 months 3 weeks ago
The Janus Kinase signalling pathway is implicated in the pathogenesis of immune-related diseases. The potency of small-molecule Janus Kinase inhibitors in the treatment of inflammatory diseases demonstrates that this pathway can be successfully targeted for therapeutic purposes. The outstanding relevant questions concerning drugs' efficacy and toxicity challenge the research to enhance the selectivity of these drugs. The promising results of computational techniques, such as Molecular Dynamics...
Michela Sperti

Modeling the structure of the frameshift-stimulatory pseudoknot in SARS-CoV-2 reveals multiple possible conformers

3 months 4 weeks ago
The coronavirus causing the COVID-19 pandemic, SARS-CoV-2, uses -1 programmed ribosomal frameshifting (-1 PRF) to control the relative expression of viral proteins. As modulating -1 PRF can inhibit viral replication, the RNA pseudoknot stimulating -1 PRF may be a fruitful target for therapeutics treating COVID-19. We modeled the unusual 3-stem structure of the stimulatory pseudoknot of SARS-CoV-2 computationally, using multiple blind structural prediction tools followed by μs-long molecular...
Sara Ibrahim Omar

Synthesis, anticancer activity and molecular docking studies of N-deacetylthiocolchicine and 4-iodo-N-deacetylthiocolchicine derivatives

3 months 4 weeks ago
Colchicine is a plant alkaloid with a broad spectrum of biological and pharmacological properties. It has found application as an anti-inflammatory agent and also shows anticancer effects through its ability to destabilize microtubules by preventing tubulin dimers from polymerizing leading to mitotic death. However, adverse side effects have so far restricted its use in cancer therapy. This has led to renewed efforts to identify less toxic derivatives. In this article, we describe the synthesis...
Greta Klejborowska

How Do Tumor-Treating Fields Work?

4 months 2 weeks ago
Since approved by the FDA for the treatment of glioblastoma brain cancer in 2015, tumor-treating fields (TTFields) have rapidly become the fourth modality to treat cancer, along with surgery, chemotherapy, and radiation [1]. TTFields are now in clinical trials for a variety of cancer types. While efficacy has been proven in the clinic, the higher efficacy is demonstrated in vitro and in animal models, which indicates much greater clinical efficacy is possible. To attain the great promise of...
Kristen W. Carlson

From quantum chemistry to quantum biology: a path toward consciousness

4 months 2 weeks ago
This paper presents a historical overview of quantum physics methodology's development and application to various science fields beyond physics, especially biology and consciousness. Following a successful interpretation of several early 20t⁢h century experiments, quantum physics gradually provided a conceptual framework for molecular bonds via quantum chemistry. In recent years individual biological phenomena such as photosynthesis and bird navigation have been experimentally and theoretically...
Jack A Tuszynski

Revealing and Attenuating the Electrostatic Properties of Tubulin and Its Polymers

5 months 1 week ago
Tubulin is an electrostatically negative protein that forms cylindrical polymers termed microtubules, which are crucial for a variety of intracellular roles. Exploiting the electrostatic behavior of tubulin and microtubules within functional microfluidic and optoelectronic devices is limited due to the lack of understanding of tubulin behavior as a function of solvent composition. This work displays the tunability of tubulin surface charge using dimethyl sulfoxide (DMSO) for the first time....
Aarat P Kalra

Non-Equilibrium Quantum Electrodynamics in Open Systems as a Realizable Representation of Quantum Field Theory of the Brain

5 months 1 week ago
We derive time evolution equations, namely the Klein-Gordon equations for coherent fields and the Kadanoff-Baym equations in quantum electrodynamics (QED) for open systems (with a central region and two reservoirs) as a practical model of quantum field theory of the brain. Next, we introduce a kinetic entropy current and show the H-theorem in the Hartree-Fock approximation with the leading-order (LO) tunneling variable expansion in the 1st order approximation for the gradient expansion. Finally,...
Akihiro Nishiyama

Tyrosine Kinase Inhibitors Reduce Glucose Uptake by Binding to an Exofacial Site on hGLUT-1: Influence on <sup>18</sup> F-FDG PET Uptake

5 months 1 week ago
Positron emission tomography (PET) using 2-deoxy-2-[^(18) F]fluoro-d-glucose ([^(18) F]FDG), a marker of energy metabolism and cell proliferation, is routinely used in the clinic to assess patient response to chemotherapy and to monitor tumor growth. Treatment with some tyrosine kinase inhibitors (TKIs) causes changes in blood glucose levels in both nondiabetic and diabetic patients. We evaluated the interaction of several classes of TKIs with human glucose transporter-1 (hGLUT-1) in FaDu and...
Vijaya L Damaraju

All Wired Up: An Exploration of the Electrical Properties of Microtubules and Tubulin

5 months 3 weeks ago
Microtubules are hollow, cylindrical polymers of the protein α, β tubulin, that interact mechanochemically with a variety of macromolecules. Due to their mechanically robust nature, microtubules have gained attention as tracks for precisely directed transport of nanomaterials within lab-on-a-chip devices. Primarily due to the unusually negative tail-like C-termini of tubulin, recent work demonstrates that these biopolymers are also involved in a broad spectrum of intracellular electrical...
Aarat P Kalra

Testing amino acid-codon affinity hypothesis using molecular docking

7 months 3 weeks ago
Genetic code refers to a set of rules that assign trinucleotides called codons to amino acids in the process of protein synthesis. Investigating the genetic code's logic and its evolutionary origin has always been both intriguing and challenging. While the correspondence rules between codons and amino acids in the genetic code are well-known, it is still unclear whether those assignments can be explained based on energetic or/and entropic arguments. As an attempt at deciphering basic...
S Arbabi Moghadam

A new method for protein characterization and classification using geometrical features for 3D face analysis: An example of tubulin structures

9 months ago
This article reports on the results of research aimed to translate biometric 3D face recognition concepts and algorithms into the field of protein biophysics in order to precisely and rapidly classify morphological features of protein surfaces. Both human faces and protein surfaces are free-forms and some descriptors used in differential geometry can be used to describe them applying the principles of feature extraction developed for computer vision and pattern recognition. The first part of...
Luca Di Grazia

New Series of Double-Modified Colchicine Derivatives: Synthesis, Cytotoxic Effect and Molecular Docking

9 months 1 week ago
Colchicine is a well-known anticancer compound showing antimitotic effect on cells. Its high cytotoxic activity against different cancer cell lines has been demonstrated many times. In this paper we report the syntheses and spectroscopic analyses of novel colchicine derivatives obtained by structural modifications at C7 (carbon-nitrogen single bond) and C10 (methylamino group) positions. All the obtained compounds have been tested in vitro to determine their cytotoxicity toward A549, MCF-7,...
Julia Krzywik

Design, synthesis and in vitro cell-free/cell-based biological evaluations of novel ERCC1-XPF inhibitors targeting DNA repair pathway

9 months 2 weeks ago
The structure-specific ERCC1-XPF endonuclease is essential for repairing bulky DNA lesions and helix distortions induced by UV radiation, which forms cyclobutane pyrimidine dimers (CPDs), or chemicals that crosslink DNA strands such as cyclophosphamide and platinum-based chemotherapeutic agents. Inhibition of the ERCC1-XPF endonuclease activity has been shown to sensitize cancer cells to these chemotherapeutic agents. In this study, we have conducted a structure activity relationship analysis...
Ahmed H Elmenoufy