Dissociation of Endohedrally Encapsulated HCl/HBr in C and C: An Electric Field Perspective.

The ability of an acid to undergo dissociation depends primarily on the nature of the solvent and especially the arrangement of the solvent molecules around the protic group. This process of acid dissociation can be promoted by confining the solute-solvent system to nanocavities. Endohedral confinement of HCl/HBr complexed with a single ammonia or a water dimer within the C/C cage results in the dissociation of mineral acid.

Unraveling topoisomerase IA gate dynamics in presence of PPEF and its preclinical evaluation against multidrug-resistant pathogens.

Type IA topoisomerases maintain DNA topology by cleaving ssDNA and relaxing negative supercoils. The inhibition of its activity in bacteria prevents the relaxation of negative supercoils, which in turn impedes DNA metabolic processes leading to cell death. Using this hypothesis, two bisbenzimidazoles, PPEF and BPVF are synthesized, selectively inhibiting bacterial TopoIA and TopoIII.

Identification of allosteric hotspots regulating the ribosomal RNA binding by antibiotic resistance-conferring Erm methyltransferases.

Antibiotic resistance via epigenetic methylation of ribosomal RNA is one of the most prevalent strategies adopted by multidrug resistant pathogens. The erythromycin-resistance methyltransferase (Erm) methylates rRNA at the conserved A2058 position and imparts resistance to macrolides such as erythromycin. However, the precise mechanism adopted by Erm methyltransferases for locating the target base within a complicated rRNA scaffold remains unclear.

Binary Matrix Method to Enumerate, Hierarchically Order, and Structurally Classify Peptide Aggregation.

Protein aggregation is a common and complex phenomenon in biological processes, yet a robust analysis of this aggregation process remains elusive. The commonly used methods such as center-of-mass to center-of-mass (COM-COM) distance, the radius of gyration (), hydrogen bonding (HB), and solvent accessible surface area do not quantify the aggregation accurately. Herein, a new and robust method that uses an aggregation matrix (AM) approach to investigate peptide aggregation in a MD simulation trajectory is presented.

Molecular Mechanism of Dual Intercalation in Sac7d-DNA Complexation.

Sac7d belongs to the hyperthermophilc chromosomal protein family, and it is very stable with regard to heat and acidic environments. Unlike many other DNA-protein complexes, the present one is a nonspecific complexation where two amino acids (AA), VAL26 and MET29, are found to intercalate into the same base pair of DNA. Here, we have carried out multiple short molecular dynamic simulations to calculate the distribution of nonspecific protein-DNA aggregates to find the most probable state, which was subsequently used to construct the free energy landscape of protein intercalation into DNA.

Ultrafast Proton-Transfer Reaction in Phenol-(Ammonia) Clusters: An Molecular Dynamics Investigation.

The ability of phenol to transfer a proton to surrounding ammonia molecules in a phenol-(ammonia) cluster depends on the relative orientation of ammonia molecules, and a critical field of about 285 MV cm is essential along the O-H bond for the proton-transfer process. MD simulations reveal that the proton-transfer process from phenol to ammonia cluster is spontaneous when the cluster has at least eight ammonia molecules, and the proton-transfer event is almost instantaneous (about 20-120 fs). These simulations also reveal that the rate-determining step for the proton-transfer process is the reorganization of the solvent around the OH group.

Characterization of a Novel Mesophilic CTP-Dependent Riboflavin Kinase and Rational Engineering to Create Its Thermostable Homologues*.

Flavins play a central role in metabolism as molecules that catalyze a wide range of redox reactions in living organisms. Several variations in flavin biosynthesis exist among the domains of life, and their analysis has revealed many new structural and mechanistic insights till date. The cytidine triphosphate (CTP)-dependent riboflavin kinase in archaea is one such example.

Molecular Mechanism of the Intercalation of the SOX-4 Protein into DNA Inducing Bends and Kinks.

DNA-protein interactions regulate several biophysical functions, yet the mechanism of only a few is investigated in molecular detail. An important example is the intercalation of transcription factor proteins into DNA that produce bent and kinked DNA. Here, we have studied the molecular mechanism of the intercalation of a transcription factor SOX4 into DNA with a goal to understand the sequence of molecular events that precede the bending and kinking of the DNA.

Molecular Origin of DNA Kinking by Transcription Factors.

Binding of transcription factor (TF) proteins with DNA may cause severe kinks in the latter. Here, we investigate the molecular origin of the DNA kinks observed in the TF-DNA complexes using small molecule intercalation pathway, crystallographic analysis, and free energy calculations involving four different transcription factor (TF) protein-DNA complexes. We find that although protein binding may bend the DNA, bending alone is not sufficient to kink the DNA.