1.
Effective lead optimization targeting the displacement of bridging receptor-ligand water molecules.
Chen, D, Li, Y, Zhao, M, Tan, W, Li, X, Savidge, T, Guo, W, Fan, X
Physical chemistry chemical physics : PCCP. 2018;(37):24399-24407
Abstract
Enhancing the binding affinities of ligands by means of lead modifications that displace bridging water molecules at protein-ligand interfaces is an important and widely studied lead optimization strategy. However, it is still challenging to ensure the success of this lead optimization strategy. Here we use theoretical derivations, which are then validated using reported experimental data, to identify the major determining factors in lead optimization designed to displace bridging water molecules. Our findings demonstrate that the nature of hydrogen-bond pairing between the ligand and protein polar atom(s) is the principal factor displacing interface water molecules, and not the binding strength of the water molecule. Our results also indicate that all interfacing bridging water molecules can potentially be targeted for displacement using this new approach. In summary, we show that strong-strong/weak-weak hydrogen-bond pairings of ligand atoms with protein atoms may provide useful guidance in lead modifications by designing modified ligands with higher binding affinities than their lead molecules. This study can help to increase the efficiency of rational drug design.
2.
Magnetic solid phase extraction of sulfonamides based on carboxylated magnetic graphene oxide nanoparticles in environmental waters.
Gao, PS, Guo, Y, Li, X, Wang, X, Wang, J, Qian, F, Gu, H, Zhang, Z
Journal of chromatography. A. 2018;:1-10
Abstract
A magnetic nano-adsorbent material was prepared by functionalizing carboxylic group onto the granule surface of magnetic graphene oxide nanoparticles (CMGO), using in-situ co-precipitating method. The surface morphology was characterized by SEM and TEM. The CMGO was selected as the adsorbent for the magnetic solid phase extraction (MSPE) of sulfonamides (SAs) from environmental water samples, and the eluted analytes were determined by ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). A series of experimental parameters were optimized to improve the extraction efficiency such as amount of CMGO, extraction time, pH, ionic strength of the sample solution and desorption conditions. When the pH of water sample was 4.00, the extraction recoveries (ERs) for SAs were over 82.0% with 15.0 mg CMGO adsorption for 20 min. Under the optimized extraction conditions, linear range was obtained with coefficients of determination (R2)≥0.9983. The limits of detection for this proposed method were in the range of 0.49-1.59 ng/L, and the enrichment factors were 1320-1702 for eight SAs. The newly developed method was successfully applied to the analysis of trace SAs in real-world water samples, which provided satisfactory ERs in the range of 82.0-106.2% with RSDs less than 7.2%. Overall, it shows a great potential for the concentration of trace amine organic pollutions in complex matrices.
3.
Alternative mechanisms for O2 release and O-O bond formation in the oxygen evolving complex of photosystem II.
Li, X, Siegbahn, PE
Physical chemistry chemical physics : PCCP. 2015;(18):12168-74
Abstract
In a previous detailed study of all the steps of water oxidation in photosystem II, it was surprisingly found that O2 release is as critical for the rate as O-O bond formation. A new mechanism for O2 release has now been found, which can be described as an opening followed by a closing of the interior of the oxygen evolving complex. A transition state for peroxide rotation forming a superoxide radical, missed in the previous study, and a structural change around the outside manganese are two key steps in the new mechanism. However, O2 release may still remain rate-limiting. Additionally, for the step forming the O-O bond, an alternative, experimentally suggested, mechanism was investigated. The new model calculations can rule out the precise use of that mechanism. However, a variant with a rotation of the ligands around the outer manganese by about 30° will give a low barrier, competitive with the old DFT mechanism. Both these mechanisms use an oxyl-oxo mechanism for O-O bond formation involving the same two manganese atoms and the central oxo group (O5).
4.
Role of hydrodynamic drag on microsphere deposition and re-entrainment in porous media under unfavorable conditions.
Li, X, Zhang, P, Lin, CL, Johnson, WP
Environmental science & technology. 2005;(11):4012-20
Abstract
Deposition and re-entrainment of 1.1 microm microspheres were examined in packed glass beads and quartz sand under both favorable and unfavorable conditions for deposition. Experiments were performed at environmentally relevant ionic strengths and flow rates in the absence of solution chemistry and flow perturbations. Numerical simulations of experimental data were performed using kinetic rate coefficients to represent deposition and re-entrainment dynamics. Deposition rate coefficients increased with increasing flow rate under favorable deposition conditions (in the absence of colloid-grain surface electrostatic repulsion), consistent with expected trends from filtration theory. In contrast, under unfavorable deposition conditions (where significant colloid-grain surface electrostatic repulsion exists), the deposition rate coefficients decreased with increasing flow rate, suggesting a mitigating effect of hydrodynamic drag on deposition. Furthermore, the re-entrainment rate was negligible under favorable conditions but was significant under unfavorable conditions and increased with increasing flow rate, demonstrating that hydrodynamic drag drove re-entrainment under unfavorable conditions. The drag torque resulting from hydrodynamic drag was found to be 1 order of magnitude or more lower than the adhesive torque based on pull-off forces from atomic force microscopy measurements. This result indicates that hydrodynamic drag was insufficient to drive re-entrainment of microspheres that were associated with the grain surface via the primary energy minimum and suggests that hydrodynamic drag drove re-entrainment of secondary-minimum-associated microspheres.
5.
[A review on the water physiological characteristics of Tamarix and its prospect].
Zeng, F, Zhang, X, Li, X
Ying yong sheng tai xue bao = The journal of applied ecology. 2002;(5):611-4
Abstract
It is very important to study and grasp the water physiological characteristics of Tamarix in order to use properly and scientifically manage it. Based on the multiply studies on the water physiological characteristics of Tamarix (P-V curves, predawn water potential and water potential daily course and transpiration rate) for many years, a preliminary comment was given on the experimental methods used at home and abroad. The aims of this paper is to understand the ecological characteristics of Tamarix as fast as possible and provide theoretical bases for the restoration and re-establishment of Tamarix in the arid and semi-arid region.