WeTICA: A directed search weighted ensemble based enhanced sampling method to estimate rare event kinetics in a reduced dimensional space.

Estimating rare event kinetics from molecular dynamics simulations is a non-trivial task despite the great advances in enhanced sampling methods. Weighted Ensemble (WE) simulation, a special class of enhanced sampling techniques, offers a way to directly calculate kinetic rate constants from biased trajectories without the need to modify the underlying energy landscape using bias potentials. Conventional WE algorithms use different binning schemes to partition the collective variable (CV) space separating the two metastable states of interest.

Clinical and Microbiological Profile of Melioidosis in a Tertiary Care Hospital in Kerala, India.

Melioidosis is a neglected tropical infection caused by the Gram-negative bacterium Burkholderia pseudomallei, which is found in soil and water across tropical countries. The infection spectrum ranges from mild localized lesions to severe sepsis. The clinical presentation, severity, and outcome are influenced by the route of infection, bacterial load, strain virulence, and specific virulence genes of B.

Temperature Dependence of Intermolecular Dynamics and Liquid Properties of Deep Eutectic Solvent, Reline.

We investigated the temperature dependence of the intermolecular dynamics, including intermolecular vibrations and collective orientational relaxation, of one of the most typical deep eutectic solvents, reline, using femtosecond Raman-induced Kerr effect spectroscopy (fs-RIKES), subpicosecond optical Kerr effect spectroscopy (ps-OKES), and molecular dynamics (MD) simulations. According to fs-RIKES results, the temperature-dependent intermolecular vibrational band peak at ∼90 cm exhibited a redshift with increasing temperature. The density-of-state (DOS) spectrum of reline by MD simulations reproduced this fs-RIKES spectral feature.

Discovery of new inhibitors of nuclease MRE11.

MRE11 nuclease is a central player in signaling and processing DNA damage, and in resolving stalled replication forks. Here, we describe the identification and characterization of new MRE11 inhibitors MU147 and MU1409. Both compounds inhibit MRE11 nuclease more specifically and effectively than the relatively weak state-of-the-art inhibitor mirin.