Designing Reaction Coordinate for Ion-Induced Pore-Assisted Mechanism of Halide Ions Permeation through Lipid Bilayer by Umbrella Sampling.

Ion permeation mechanism through lipid membranes helps to understand cellular processes. We propose new reaction coordinates that allow ions to permeate according to their water affinity and interaction with the hydrophilic layer. Simulations were done for three different halides (F, Cl, and I) in two different lipid bilayers, 1,2-dipalmitoyl--glycero-3-phosphocholine (DPPC) and 1,2-dinervonoyl--glycero-3-phosphocholine (DNPC).

Exploring the Barriers in the Aggregation of a Hexadecameric Human Prion Peptide through the Markov State Model.

The prefibrillar aggregation kinetics of prion peptides are still an enigma. In this perspective, we employ atomistic molecular dynamics (MD) simulations of the shortest human prion peptide (HPP) (GYMLGS) at various temperatures and peptide concentrations and apply the Markov state model to determine the various intermediates and lag phases. Our results reveal that the natural mechanism of prion peptide self-assembly in the aqueous phase is impeded by two significant kinetic barriers with oligomer sizes of 6-9 and 12-13 peptides, respectively.

Influence of Ion Specificity and Concentration on the Conformational Transition of Intrinsically Disordered Sheep Prion Peptide.

The structural sensitivity of the intrinsically disordered proteins with the ions has been observed experimentally; however, it is still unclear how the presence of different metal ions affects structural stability. We performed an atomistic molecular dynamics simulation of sheep prion peptide (142-167) in presence of different monovalent, divalent ions at various concentrations to find out the effect of the size, charge, and ionic concentration on the structure of the peptide. It is found that Li ions have a higher survival probability compared to Na , K and Mg affecting the solvation structure of the protein leading to the alpha-helix structure.

Deciphering the competitive inhibition of dihydropteroate synthase by 8 marcaptoguanine analogs: enhanced potency in phenylsulfonyl fragments.

The emergence of sulfa-drug resistance and reduced efficacy of pterin-based analogs towards Dihydropteroate synthase (DHPS) inhibition dictate a pressing need of developing novel antimicrobial agents for immune-compromised patients. Recently, a series of 8-Marcaptoguanin (8-MG) derivatives synthesized for 6-Hydroxymethyl-7,8-dihydropterin pyrophosphokinase (experimental K ∼ 100-.0.

Epitope-Based Potential Vaccine Candidate for Humoral and Cell-Mediated Immunity to Combat Severe Acute Respiratory Syndrome Coronavirus 2 Pandemic.

The emergence of severe acute respiratory syndrome from novel Coronavirus (SARS-CoV-2) has put an immense pressure worldwide where vaccination is believed to be an efficient way for developing hard immunity. Herein, we employ immunoinformatic tools to identify B-cell, T-cell epitopes associated with the spike protein of SARS-CoV-2, which is important for genome release. The results showed that the highly immunogenic epitopes located at the stalk part are mostly conserved compared to the receptor binding domain (RDB).

Computational insights into factor affecting the potency of diaryl sulfone analogs as Escherichia coli dihydropteroate synthase inhibitors.

Dihydropteroate synthase (DHPS) is an alluring target for designing novel drug candidates to prevent infections caused by pathogenic Escherichia coli strains. Diaryl Sulfone (SO) compounds are found to inhibit DHPS competitively with respect to the substrate pABA (p-aminobenzoate). The extra aromatic ring of diaryl sulfone compounds found to stabilize them in highly flexible pABA binding loops.