Anti-tau antibodies targeting a conformation-dependent epitope selectively bind seeds.

Neurodegenerative tauopathies are caused by the transition of tau protein from a monomer to a toxic aggregate. They include Alzheimer disease (AD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and Pick disease (PiD). We have previously proposed that tau monomer exists in two conformational ensembles: an inert form (M), which does not self-assemble, and seed-competent form (M), which self-assembles and templates ordered assembly growth.

FTD-tau S320F mutation stabilizes local structure and allosterically promotes amyloid motif-dependent aggregation.

Amyloid deposition of the microtubule-associated protein tau is associated with neurodegenerative diseases. In frontotemporal dementia with abnormal tau (FTD-tau), missense mutations in tau enhance its aggregation propensity. Here we describe the structural mechanism for how an FTD-tau S320F mutation drives spontaneous aggregation, integrating data from in vitro, in silico and cellular experiments.

Arylcoumarin perturbs SARS-CoV-2 pathogenesis by targeting the S-protein/ACE2 interaction.

The vaccination drive against COVID-19 worldwide was quite successful. However, the second wave of infections was even more disastrous. There was a rapid increase in reinfections and human deaths due to the appearance of new SARS-CoV-2 variants.

Computational Insights of Unfolding of N-Terminal Domain of TDP-43 Reveal the Conformational Heterogeneity in the Unfolding Pathway.

TDP-43 proteinopathies is a disease hallmark that characterizes amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). The N-terminal domain of TDP-43 (NTD) is important to both TDP-43 physiology and TDP-43 proteinopathy. However, its folding and dimerization process is still poorly characterized.

Exploring the interaction mechanism between potential inhibitor and multi-target Mur enzymes of mycobacterium tuberculosis using molecular docking, molecular dynamics simulation, principal component analysis, free energy landscape, dynamic cross-correlation matrices, vector movements, and binding free energy calculation.

Multi-targeting enzyme approaches are considered to be the most significant in suppressing pathogen growth and disease control for MDR and XDR-resistant . The multiple Mur enzymes involved in peptidoglycan biosynthesis play a key role in a cell's growth. Firstly, homology modeling was employed to construct the 3 D structure of the Mur enzymes.

Combination therapy of biogenic C-dots and lysozyme for enhanced antibacterial and antibiofilm activity.

Nearly 80% of human chronic infections are caused due to bacterial biofilm formation. The increased resistance against the conventional antimicrobial agents makes it difficult to treat the biofilm-related infections. The antibiotics resistance developed by planktonic cells has also become a major threat for human.

Delineating the conformational dynamics of intermediate structures on the unfolding pathway of β-lactoglobulin in aqueous urea and dimethyl sulfoxide.

The funnel shaped energy landscape model of the protein folding suggests that progression of folding proceeds through multiple pathways, having the multiple intermediates which leads to multidimensional free-energy surface. Herein, we applied all-atom MD simulation to conduct a comparative study on the structure of β-lactoglobulin (β-LgA) in aqueous mixture of 8 M urea and 8 M dimethyl sulfoxide (DMSO), at different temperatures. The cumulative results of multiple simulations suggest a common unfolding pathway of β-LgA, occurred through the stable and meta-stable intermediates (I), in both urea and DMSO.

Solvent sensitivity of protein aggregation in Cu, Zn superoxide dismutase: a molecular dynamics simulation study.

Misfolding and aggregation of Cu, Zn Superoxide Dismutase (SOD1) is often found in amyotrophic lateral sclerosis (ALS) patients. The central apo SOD1 barrel was involved in protein maturation and pathological aggregation in ALS. In this work, we employed atomistic molecular dynamics (MD) simulations to study the conformational dynamics of SOD1 monomer in different concentrations of trifluoroethanol (TFE).

Elucidation of stable intermediates in urea-induced unfolding pathway of human carbonic anhydrase IX.

Human carbonic anhydrase IX (CAIX) has evolved as a promising biomarker for cancer prognosis, due to its overexpression in various cancers and restricted expression in normal tissue. However, limited information is available on its biophysical behavior. The unfolding of CAIX in aqueous urea solution was studied using all-atom molecular dynamics simulation approach.