Stability of complex biotherapeutics like monoclonal antibodies is paramount for their safe and efficacious use. Excipients are inactive ingredients that added to the purified product so as offer it a stable environment. Trehalose dihydrate non-reducing sugar commonly used stabilizing agent in biotherapeutic formulations under liquid frozen states. The effect trehalose against aggregation protein well known. present study aims insights into stability effects higher concentration (230 mM) on...

Toxicity prediction of chemical compounds is a grand challenge. Lately, it achieved significant progress in accuracy but using huge set features, implementing complex blackbox technique such as deep neural network, and exploiting enormous computational resources. In this paper, we strongly argue for the models methods that are simple machine learning characteristics, efficient computing resource usage, powerful to achieve very high levels. To demonstrate this, develop single task-based...

The advent of human genome sequencing project has led to a spurt in the number protein sequences databanks. Success structure based drug discovery severely hinges on availability structures. Despite significant progresses area experimental determination, sequence-structure gap is continually widening. Data driven homology computational methods have proved successful predicting tertiary structures for sharing medium high sequence similarities. With dwindling similarities query sequences,...

RNA-dependent RNA polymerase (RdRp), also called nsp12, is considered a promising but challenging drug target for inhibiting replication and hence, the growth of various RNA-viruses. In this report, computational study performed to offer insights on binding Remdesivir Galidesivir with SARS-CoV2 RdRp natural substrate, ATP, as control. It was observed that exhibited similar energies their best docked poses, −6.6 kcal/mole −6.2 kcal/mole, respectively. ATP displayed comparative strong free...

Toxicity prediction using quantitative structure–activity relationship has achieved significant progress in recent years. However, most existing machine learning methods toxicity utilize only one type of feature representation and neural network, which essentially restricts their performance. Moreover, that use more than struggle with the aggregation information captured within features since they predetermined formulas. In this paper, we propose a deep framework for five individual base...

Host cell proteins (HCPs) are considered a critical quality attribute and linked to safety efficacy of biotherapeutic products. Researchers have identified 10 HCPs in Chinese hamster ovary (CHO) that exhibit common characteristics product association, coelution, age‐dependent expression therefore “difficult remove” during downstream purification. These include cathepsin D, clusterin, galectin‐3‐binding protein, G‐protein coupled receptor 56, lipoprotein lipase, metalloproteinase inhibitor,...

We report a structure-based approach to design peptides that can bind aggregation-prone, partially folded intermediates (PFI) of insulin, thereby inhibiting early stages aggregation nucleation. account for the important role modular architecture protein-protein binding interfaces and tertiary structure heterogeneity PFIs in peptide inhibitors. The determination association hotspots revealed two interface segments are required capture majority contribution insulin homodimer energy. selection...

The biggest challenge in medical management and control of the COVID-19 pandemic is nonavailability treatment molecules. While vaccines other biotherapeutic products for managing have reached market, a small-molecule cure yet to be developed. This relevant because cost production, storage, ease distribution drug are significantly more favorable than those biologics. In this paper, we present multicompound approach, where two molecules administered concurrently offer an effective therapy...

The arrangement of amino acids in a protein sequence encodes its native folding. However, the same aggregation-prone regions may cause misfolding as result local environmental stress. Under normal physiological conditions, such congregate protein's interior to avoid aggregation and attain fold. We have used solvent accessibility patches (SAAPp) determine packing residues. Our results showed that SAAPp has low values for crystal structures, consistent with folding mechanism minimize also...

The term "interpretability" is oftenly used by machine learning researchers each with their own intuitive understanding of it. There no universal well agreed upon definition interpretability in learning. As any type science discipline mainly driven the set formulated questions rather than different tools that discipline, e.g. astrophysics learns composition stars, not as use spectroscopes. Similarly, we propose should be a answers specific related to interpretability. These can statistical,...

Abstract Diagnostics has played a significant role in effective management of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Nucleocapsid protein (N protein) is the primary antigen virus for development sensitive diagnostic assays. Thus far, limited knowledge exists about antigenic properties N protein. In this paper, we demonstrate impact dimerization SARS-CoV-2 nucleocapsid on sensitivity enzyme-linked immunosorbent assay (ELISA) based diagnostics COVID-19. The expressed...

<title>Abstract</title> Neuraminidase (NA) is an essential enzyme located at the outer layer of influenza virus and plays a key role in release virions. This study aims to identify analyze possible inhibitors NA from different subtypes viruses, especially considering global outbreaks that highlight immediate requirement for effective antiviral drugs. Initially, thorough search was conducted Protein Data Bank (PDB) gather structures proteins were attached with oseltamivir, widely recognized...

ABSTRACT: The Marburg virus (MARV) causes severe hemorrhagic fevers with life-threatening symptoms. A study aimed to design a multi-epitope vaccine (MEV) using immunoinformatic approaches for treatment MARV infection. comprehensive screening procedure was used identify immunogenic protein sequences within seven crucial proteins from that could trigger T-cell and B-cell responses. computational analysis of these epitopes showed non-allergenic nature significant antigenicity, validating the...

Biosimilars offer an avenue for potential cost savings and enhanced patient access to various emerging therapies in a budget neutral way. of the granulocyte colony stimulating factor (GCSF) are excellent example this regard with as many 18 versions drug being currently approved across globe treatment neutropenia. Here, we identified oxidation methionine residues GCSF key heterogeneity that adversely impact its efficacy. In agreement earlier studies, it was found Met 122 127 significantly...