We review major computational chemistry techniques applied in industrial enzyme studies, especially approaches intended for guiding enzyme engineering. These include molecular mechanics force field and molecular dynamics simulation, quantum mechanical and combined quantum mechanical/molecular mechanical approaches, electrostatic continuum models, molecular docking, etc. These approaches are essentially introduced from the following two angles for viewing: one is about the methods themselves, including the basic concepts, the primary computational results, and potential advantages and limitations; the other is about obtaining valuable information from the respective calculations to guide the design of mutants and mutant libraries.
Enzymes ; chemistry ; genetics ; metabolism ; Molecular Docking Simulation ; Molecular Dynamics Simulation ; Mutant Proteins ; chemistry ; genetics ; metabolism ; Protein Engineering ; Quantum Theory ; Static Electricity

Measuring discomfort towardthe car seat is important as the act of driving requires a driver to remain at the car seat while controlling the car. The seat condition, including sitting position as well as the driver’s posture can lead to discomfort and fatigue. The objective of this study is to investigate a driver’s pressure distribution in static and dynamic circumstances for two types of cars; the sedan and compact car. This study involved both subjective and objective evaluations of 12 respondents. For the subjective evaluation, the Visual Analog Scales (VAS) were used to obtain respondents' perception of discomfort. For the objective evaluation, pressure distribution readings of the seat interface were obtained using piezo capacitive sensors. The findings showed that the highest pressure was recorded for the compact car. Furthermore, the static circumstance showed greater pressure compared to the dynamic state. Subjective evaluation indicated that the right buttocks and the lower back (lumbar)experience the highest discomfort for both types of seats.The type of seat found to contribute to the value of different pressure. Thus, it can be concluded that appropriate seat selection can reduce pressure as well as discomfort.
Pressure ; car seat ; back rest ; static ; dynamic ; sedan ; compact

The effect of surface charges on the cellular uptake rate and drug release profile of tetrandrine-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (TPNs) was studied. Stabilizer-free nanoprecipitation method was used in this study for the synthesis of TPNs. A typical layer-by-layer approach was applied for multi-coating particles' surface with use of poly(styrene sulfonate) sodium salt (PSS) as anionic layer and poly(allylamine hydrochloride) (PAH) as cationic layer. The modified TPNs were characterized by different physicochemical techniques such as Zeta sizer, scanning electron microscopy and transmission electron microscopy. The drug loading efficiency, release profile and cellular uptake rate were evaluated by high performance liquid chromatography and confocal laser scanning microscopy, respectively. The resultant PSS/PAH/PSS/PAH/TPNs (4 layers) exhibited spherical-shaped morphology with the average size of 160.3±5.165 nm and zeta potential of-57.8 mV. The encapsulation efficiency and drug loading efficiency were 57.88% and 1.73%, respectively. Multi-layer coating of polymeric materials with different charges on particles' surface could dramatically influence the drug release profile of TPNs (4 layers vs. 3 layers). In addition, variable layers of surface coating could also greatly affect the cellular uptake rate of TPNs in A549 cells within 8 h. Overall, by coating particles' surface with those different charged polymers, precise control of drug release as well as cellular uptake rate can be achieved simultaneously. Thus, this approach provides a new strategy for controllable drug delivery.
Antineoplastic Agents, Phytogenic ; administration & dosage ; chemistry ; Benzylisoquinolines ; administration & dosage ; chemistry ; Cell Line, Tumor ; Drug Liberation ; Humans ; Lactic Acid ; chemistry ; Nanoparticles ; adverse effects ; chemistry ; metabolism ; Polyamines ; chemistry ; Polyglycolic Acid ; chemistry ; Polystyrenes ; chemistry ; Static Electricity

The human pregnane X receptor (hPXR) plays a critical role in the metabolism, transport and clearance of xenobiotics in the liver and intestine. The hPXR can be activated by a structurally diverse of drugs to initiate clinically relevant drug-drug interactions. In this article, in silico investigation was performed on a structurally diverse set of drugs to identify critical structural features greatly related to their agonist activity towards hPXR. Heuristic method (HM)-Best Subset Modeling (BSM) and HM-Polynomial Neural Networks (PNN) were utilized to develop the linear and non-linear quantitative structure-activity relationship models. The applicability domain (AD) of the models was assessed by Williams plot. Statistically reliable models with good predictive power and explain were achieved (for HM-BSM, r (2)=0.881, q LOO (2) =0.797, q EXT (2) =0.674; for HM-PNN, r (2)=0.882, q LOO (2) =0.856, q EXT (2) =0.655). The developed models indicated that molecular aromatic and electric property, molecular weight and complexity may govern agonist activity of a structurally diverse set of drugs to hPXR.
Computer Simulation ; Humans ; Models, Statistical ; Molecular Weight ; Neural Networks (Computer) ; Quantitative Structure-Activity Relationship ; Receptors, Steroid ; agonists ; chemistry ; Small Molecule Libraries ; chemistry ; Static Electricity

Antiviral Agents ; chemistry ; metabolism ; Crystallography, X-Ray ; Ligands ; Protein Binding ; Protein Structure, Tertiary ; RNA Helicases ; chemistry ; classification ; metabolism ; Static Electricity ; Viral Proteins ; chemistry ; classification ; metabolism ; Zika Virus ; enzymology

This article presents several common problems.of medical injection pump through one case of ESD troubleshooting. Expounds the causes of the problem and provides solutions.
Equipment and Supplies ; Injections ; instrumentation ; Static Electricity

Unlike the well-established picture for the entry of enveloped viruses, the mechanism of cellular entry of non-enveloped eukaryotic viruses remains largely mysterious. Picornaviruses are representative models for such viruses, and initiate this entry process by their functional receptors. Here we present the structural and functional studies of SCARB2, a functional receptor of the important human enterovirus 71 (EV71). SCARB2 is responsible for attachment as well as uncoating of EV71. Differences in the structures of SCARB2 under neutral and acidic conditions reveal that SCARB2 undergoes a pivotal pH-dependent conformational change which opens a lipid-transfer tunnel to mediate the expulsion of a hydrophobic pocket factor from the virion, a pre-requisite for uncoating. We have also identified the key residues essential for attachment to SCARB2, identifying the canyon region of EV71 as mediating the receptor interaction. Together these results provide a clear understanding of cellular attachment and initiation of uncoating for enteroviruses.
Acids ; chemistry ; Amino Acid Sequence ; Animals ; Capsid Proteins ; chemistry ; genetics ; metabolism ; Enterovirus A, Human ; genetics ; metabolism ; physiology ; HEK293 Cells ; Host-Pathogen Interactions ; Humans ; Hydrogen-Ion Concentration ; Lysosome-Associated Membrane Glycoproteins ; chemistry ; genetics ; metabolism ; Molecular Docking Simulation ; Molecular Sequence Data ; Protein Binding ; Protein Conformation ; Protein Interaction Mapping ; Protein Structure, Tertiary ; RNA, Viral ; genetics ; metabolism ; Receptors, Scavenger ; chemistry ; genetics ; metabolism ; Sequence Homology, Amino Acid ; Sf9 Cells ; Static Electricity ; Virion ; genetics ; metabolism ; Virus Attachment

Cell Adhesion ; Cell Proliferation ; Cells, Cultured ; Chitosan ; chemistry ; Coated Materials, Biocompatible ; Collagen ; chemistry ; Humans ; Materials Testing ; Polyethyleneimine ; chemistry ; Static Electricity ; Surface Properties ; Titanium ; chemistry

To develop standard in vitro chondrosarcoma models, we synthesized three hydrogels (i. e., PDMAAm, PNaAMPS and PMETAC) and investigated the influence of Young's modulus, swelling ratio and electric charges on the behavior of chondrosarcoma cells seeded on the hydrogels, including morphology, adhesion and aggregation. Results showed that the morphology of chondrosarcoma cells at 6h was dependent on the charges of hydrogels; cells present spindle-shaped and round-shaped morphology on negative charged and neutral hydrogel, respectively, while no cells spreaded on positive charged hydrogel. Chondrosarcoma cells formed aggregates on neutral PDMAAm after further culture. The hydrogels can be synthesized easily and has the characteristics of ease at use with defined components, which holds great potential for developing standard chondrosarcoma models in vitro.
Bone Neoplasms ; pathology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Chondrosarcoma ; pathology ; Humans ; Hydrogels ; chemistry ; pharmacology ; Methacrylates ; pharmacology ; Nylons ; pharmacology ; Static Electricity

The F-BAR domain containing proteins PACSINs are cytoplasmic phosphoproteins involved in various membrane deformations, such as actin reorganization, vesicle transport and microtubule movement. Our previous study shows that all PACSINs are composed of crescent shaped dimers with two wedge loops, and the wedge loop-mediated lateral interaction between neighboring dimers is important for protein packing and tubulation activity. Here, from the crystal packing of PACSIN 2, we observed a tight tip-to-tip interaction, in addition to the wedge loop-mediated lateral interaction. With this tip-to-tip interaction, the whole packing of PACSIN 2 shows a spiral-like assembly with a central hole from the top view. Elimination of this tip-to-tip connection inhibited the tubulation function of PACSIN 2, indicating that tip-to-tip interaction plays an important role in membrane deformation activity. Together with our previous study, we proposed a packing model for the assembly of PACSIN 2 on membrane, where the proteins are connected by tip-to-tip and wedge loop-mediated lateral interactions on the surface of membrane to generate various diameter tubules.
Adaptor Proteins, Signal Transducing ; chemistry ; genetics ; Cell Membrane ; chemistry ; Crystallography, X-Ray ; Humans ; Liposomes ; chemistry ; Models, Molecular ; Mutagenesis, Site-Directed ; Protein Interaction Domains and Motifs ; Protein Multimerization ; Protein Structure, Quaternary ; Recombinant Proteins ; chemistry ; genetics ; Static Electricity