Physical scoring function based on AMBER force field and Poisson-Boltzmann implicit solvent for protein structure prediction

A well-behaved physics-based all-atom scoring function for protein structure prediction is analyzed with several widely used all-atom decoy sets. The scoring function, termed AMBER/Poisson-Boltzmann (PB), is based on a refined AMBER force field for intramolecular interactions and an efficient PB model for solvation interactions. Testing on the chosen decoy sets shows that the scoring function, which is designed to consider detailed chemical environments, is able to consistently discriminate all 62 native crystal structures after considering the heteroatom groups, disulfide bonds, and crystal packing effects that are not included in the decoy structures. When NMR structures are considered in the testing, the scoring function is able to discriminate 8 out of 10 targets. In the more challenging test of selecting near-native structures, the scoring function also performs very well: for the majority of the targets studied, the scoring function is able to select decoys that are close to the corresponding native structures as evaluated by ranking numbers and backbone Calpha root mean square deviations. Various important components of the scoring function are also studied to understand their discriminative contributions toward the rankings of native and near-native structures. It is found that neither the nonpolar solvation energy as modeled by the surface area model nor a higher protein dielectric constant improves its discriminative power. The terms remaining to be improved are related to 1-4 interactions. The most troublesome term is found to be the large and highly fluctuating 1-4 electrostatics term, not the dihedral-angle term. These data support ongoing efforts in the community to develop protein structure prediction methods with physics-based potentials that are competitive with knowledge-based potentials.     

Do the effects of piscivorous largemouth bass cascade to the plankton?

Ecologists have hypothesized that an increase in the biomass of piscivorous fish in lakes will cause a decrease in populations of planktivorous fish, an increase in the size of herbivorous zooplankton and a decrease in the biomass of phytoplankton. Here we present an experimental test of whether the effects of largemouth bass (Micropterus salmoides) cascade to the planktivorous fish, zooplankton and phytoplankton of a 15-ha water storage reservoir. A pilot study indicated that the reservoir was eutrophic with dense populations of planktivorous fish dominated by threadfin shad (Dorosoma petenense). No piscovorous fish were present in the reservoir. We conducted a one-month mesocosm experiment using water and plankton from the reservoir showing that the presence of threadfin shad reduced large-sized zooplankton and increased the productivity and biomass of phytoplankton. To test whether the effects of piscivorous fish could cascade to the plankton, we assessed the effects of the addition of piscivorous largemouth bass on the planktivorous fish, zooplankton and biomass of phytoplankton of the reservoir by monitoring the reservoir during the year before and the two years after largemouth bass were stocked. In the second year after the addition of largemouth bass, the number of planktivorous fish decreased and the relative abundance of threadfin shad declined. Although the abundance of cladocerans increased after the addition of largemouth bass, the average size of zooplankton did not change. We did not detect changes in chlorophyll a, Secchi depth, or concentrations of total phosphorus and total nitrogen as a result of the addition of largemouth bass.     

Endogenous protease mediated manifestation of a Ca2+-stimulated ATPase in purified dog gastric microsomes

An endogenous soluble protease has been demonstrated to unmask a Ca²⁺-stimulated ATPase activity in purified dog gastric microsomes. The presence of ATP during protease treatment appears essential for the manifestation of the gastric Ca²⁺-stimulated ATPase activity. The endogenous protease appears to have trypsin-like activity, since soybean trypsin inhibitor completely blocks the protease effect. Manifestation of the Ca²⁺-stimulated ATPase occurs without affecting the microsomal (H⁺ +K⁺)-ATPase activity and associated H⁺ uptake ability. The unmasked Ca²⁺-stimulated ATPase appears insensitive to calmodulin. Possible roles of the enzyme in the regulation of gastric H⁺ transport have been discussed.     

Amino acid-based enantiomerically pure 3-substituted 1,4-benzodiazepin-2-ones: a new class of anti-ischemic agents

A series of 3-substituted 1,4-benzodiazepin-2-ones derived from S and R amino acids were evaluated for their anti-ischemic activity in vitro. Treatment with compounds 7h, 16, 9d, and 17 decreased the apoptotic neuronal number, however increased the neuronal viability. The compounds decreasing apoptosis could protect neurons from the ischemic injury. The difference in the activities of 1,4-benzodiazepin-2-ones derived from S- and R-amino acids is discussed and explained on the basis of molecular modeling studies.