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Poisson-Boltzmann electrostatics is a well established model in biophysics; however, its application to large-scale biomolecular processes such as protein-protein encounter is still limited by the efficiency and memory constraints of existing numerical techniques. In this article, we present an efficient and accurate scheme that incorporates recently developed numerical techniques to enhance our computational ability. In particular, a boundary integral equation approach is applied to discretize the linearized Poisson-Boltzmann equation; the resulting integral formulas are well conditioned and are extended to systems with arbitrary numbers of biomolecules. The solution process is accelerated by Krylov subspace methods and a new version of the fast multipole method. In addition to the electrostatic energy, fast calculations of the forces and torques are made possible by using an interpolation procedure. Numerical experiments show that the implemented algorithm is asymptotically optimal O(N) in both CPU time and required memory, and application to the acetylcholinesterase-fasciculin complex is illustrated.

The gating motion of the human nicotinic acetylcholine receptor (nAChR) alpha 7 was investigated with normal mode analysis (NMA) of two homology models. The first model, referred to as model 1, was built from both the Lymnaea stagnalis acetylcholine binding protein (AChBP) and the transmembrane (TM) domain of the Torpedo marmorata nAChR. The second model, referred to as model C, was based solely on the recent electron microscopy structure of the T. marmorata nAChR. Despite structural differences, both models exhibit nearly identical patterns of flexibility and correlated motions. In addition, both models show a similar global twisting motion that may represent channel gating. The similar results obtained for the two models indicate that NMA is most sensitive to the contact topology of the structure rather than its finer detail. The major difference between the low-frequency motions sampled for the two models is that a symmetrical pore-breathing motion, favoring channel opening, is present as the second most dominant motion in model 1, whilst largely absent from model C. The absence of this mode in model C can be attributed to its less symmetrical architecture. Finally, as a further goal of the present study, an approximate open channel model, consistent with many experimental findings, has been produced. (c) 2005 Elsevier Ltd. All rights reserved.

The electrostatic interaction among molecules solvated in ionic solution is governed by the Poisson-Boltzmann equation (PBE). Here the hypersingular integral technique is used in a boundary element method (BEM) for the three-dimensional (3D) linear PBE to calculate the Maxwell stress tensor on the solvated molecular surface, and then the PB forces and torques can be obtained from the stress tensor. Compared with the variational method (also in a BEM frame) that we proposed recently, this method provides an even more efficient way to calculate the full intermolecular electrostatic interaction force, especially for macromolecular systems. Thus, it may be more suitable for the application of Brownian dynamics methods to study the dynamics of protein/protein docking as well as the assembly of large 3D architectures involving many diffusing subunits. The method has been tested on two simple cases to demonstrate its reliability and efficiency, and also compared with our previous variational method used in BEM. (c) 2005 American Institute of Physics.

C18H21NO8S, monoclinic, P121/c1 (no. 14), a = 21.069(5) Å, b = 11.494(3)Å, c = 7.996(2)Å, β = 97.257(3)°, V = 1920.9Å3, Z = 4, Rgt(F) = 0.044, wRref(F2) = 0.124, T = 298 K.

Objective: To analyze the gene variation of a genetic coagulation factor Ⅴ (FⅤ) deficiency pedigree and explore the molecular pathogenesis. Methods: The proband was a 32 years old female. The patient was prone to nose bleeding since childhood which was usually self-healed. On March 10, 2021, the proband went to the First Affiliated Hospital of Air Force Medical University for treatment of knee hematoma caused by a fall. None of the family members reported any history of bleeding. The prothrombin time (PT), activated partial thromboplastin time (APTT) and FⅤ activity (FⅤ: C) were detected by clotting method and the FⅤ antigen (FⅤ: Ag) was tested with enzyme-linked immunosorbent assay (ELISA). All exons and flanks of F5 gene were determined by Sanger sequencing. Clustalx-2.1-win, PolyPhen-2 and Swiss-PDBViewer software were used to analyze the conservatism of missense variation sites, whether the variations were harmful and their influences on protein structure and function. MutationTaster and NetGene2 software were used to analyze whether the splice site variation was harmful and its effect on the splice site. Results: The PT and APTT of the proband prolonged to 24.0 s and 69.8 s, respectively. The FⅤ: C and FⅤ: Ag decreased to 6% and 9%, respectively. There were compound heterozygous variations in F5 gene, which included c.911G>A heterozygous missense variation in exon 6 leading to p.Gly276Glu variation and c.5208+1G>A heterozygous missense variation in intron 15. The father and daughter had the p.Gly276Glu heterozygous variation. Her mother and son had the c.5208+1G>A heterozygous variation. Software analysis results of p.Gly276Glu heterozygous variation showed that Gly276 was conserved among homologous species, the variation was harmful, and it could affect the local structure and function of the protein. The c.5208+1G>A heterozygous variation was deleterious and resulted in the disappearance of the splice site, thereby affecting the protein function. Conclusion: The p.Gly276Glu and c.5208+1G>A compound heterozygous variants are deleterious variants associated with the patient's disease and may be the molecular pathogenesis of inherited FⅤ deficiency in this family.

Bacterial mercury oxidation coupled to denitrification offers great potential for simultaneous removal of elemental mercury (Hg 0 ) and nitric oxide (NO) in a denitrifying membrane biofilm reactor (MBfR). Four potentially contributory mechanisms tested separately, namely, membrane gas separation, medium absorption, biosorption and biotransformation, which contributed 4.9%/7.2%, 8.1%/8.9%, 38.8%/9.5% and 48.2%/84.9% of overall Hg 0 /NO removal in MBfR. Herein, Hg 0 bio-oxidation, oxidative Hg 0 biosorption and denitrification played leading roles in simultaneous removal of Hg 0 and NO. Living microbes performed simultaneous Hg 0 bio-oxidation and denitrification, in which Hg 0 as electron donor was biologically oxidized to oxidized mercury (Hg 2+ ), while NO as the terminal electron acceptor was denitrified to N 2 . The Hg 2+ further complexed with humic acids in extracellular polymeric substances via functional groups (-SH, -OH, -NH - and -COO - ) and formed humic acids bound mercury (HA-Hg). Non-living microbial matrix performed oxidative Hg 0 biosorption, in which Hg 0 may be physically adsorbed by cellular matrix, then non-metabolically oxidized to Hg 2+ via oxidative complexation with -SH in humic acids and finally cleavage of S-H bond and surface charge transfer led to formation of HA-Hg. Therefore, bioconversion of Hg 0 to HA-Hg by Hg 0 bio-oxidation and oxidative Hg 0 biosorption coupled with NO denitrification to N 2 dynamically cooperated to accomplish simultaneous removal of Hg 0 and NO in MBfR., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Photocatalytic membrane coupled to biodegradation offers potential for degrading volatile organic compounds (VOCs) in photocatalytic membrane biofilm reactor. An intimately coupled photocatalysis and biodegradation reactor was operated in continuous operation for 500 days to treat simulated waste gas containing toluene. Toluene removal efficiency obtained 99%, with the elimination capacity of 550 g m -3 ·h -1 . Membrane photocatalysis coupled to biodegradation was created to improve toluene removal from 11 to 20%. The dominant genera were Lysinibacillus, Hydrogenophaga, Pseudomonas at 30 d, Rudaea, Dongia, Litorilinea at 230 d xyl, Tod, Tcb, Bed, Tmo, Tbu, Tou, Dmp, Cat were functional genes of toluene metabolism, as shown by16S rDNA and metagenomic sequencing. Photocatalysis destroyed part of the toluene into biodegradable intermediates that were immediately mineralized by microorganisms in biofilm, some toluene was directly degraded by toluene degrading bacterial community into carbon dioxide and water. The novel hybrid photocatalytic membrane biofilm reactor is a cost-effective and robust alternative to VOCs treatment., (Copyright © 2019. Published by Elsevier Inc.)

Objective: To investigate the relationship between sex hormones and metabolic syndrome (MS), as well as its components in elderly men., Methods: 1 505 elderly men (≥60 years old, mean age 75.4±9.7 years old) who participated in a routine health screening examination in PLA general hospital from May to June in 2012 were enrolled in this cross-sectional study. Serum lipids, glucose and sex hormones were measured along with body height, weight and blood pressure. Free testosterone (FT) and bioavailable testosterone (BT) were calculated. The correlation of serum sex hormones with the presence of MS and its components were analyzed., Results: The prevalence of MS was 21.7% (326/1 505) in this study. Elderly men with MS had lower levels of sex hormone-binding globulin (SHBG), total testosterone (TT), FT and BT than those without MS. The levels of SHBG, TT, FT and BT were significantly lower in the overweight/obesity group, hyperglycemia group and dyslipidemia group than those in the respective control groups (P<0.05). Logistic regression analysis showed that the SHBG level was an independent risk factor for MS in elderly men(OR=0.977, 95%CI: 0.964-0.989, P<0.001), while the levels of TT, FT and BT were not associated with MS. The prevalence of MS gradually increased with decreasing of SHBG values (P<0.001). When comparing subjects in the lowest and highest quartile of SHBG, the former group demonstrated a 2.13-fold increase in the odds ratio for MS after adjusting for age, smoking, drinking and other sex hormone indices., Conclusion: In elderly men, lower SHBG level, not TT, FT or BT may be an independent predictor for the prevalence of MS, in which the mechanism requires further studies.

The reaction mechanisms of two inhibitor TFK(+) and TFK(0) binding to H447I mutant mouse acetylcholinesterase (mAChE) have been investigated by using a combined ab initio quantum mechanical/molecular mechanical (QM/MM) approach and classical molecular dynamics (MD) simulations. TFK(+) binding to the H447I mutant may proceed with a different reaction mechanism from the wild-type. A water molecule takes over the role of His447 and participates in the bond breaking and forming as a "charge relayer". Unlike in the wild-type mAChE case, Glu334, a conserved residue from the catalytic triad, acts as a catalytic base in the reaction. The calculated energy barrier for this reaction is about 8kcal/mol. These predictions await experimental verification. In the case of the neutral ligand TFK(0), however, multiple MD simulations on the TFK(0)/H447I complex reveal that none of the water molecules can be retained in the active site as a "catalytic" water. Taken together our computational studies confirm that TFK(0) is almost inactive in the H447I mutant, and also provide detailed mechanistic insights into the experimental observations.

This paper describes a high performance liquid chromatographic method for analysis of organic additives in copper-plating brightener. The copper-plating brightener was filtered through 0.45 microgram micropore membrane and determined on a Spherisorb-C6H5 column, with V(methanol):V(water) = 30:70 mobile phase at the flow rate of 1.5 mL/min, and detected at UV 210 nm. 2-benzimidazolethiol, ethylene thiourea, 1-propanesulfonic acid 3,3'-dithio-bis-disodium salt were separated and determined. The recoveries were more than 99% with CV less than 1%. The method is simple and rapid.