Intrinsically disordered proteins (IDPs) are closely related to various human diseases. Because IDPs lack certain tertiary structure, it is difficult to use X-ray and NMR methods to measure their structures. Therefore, molecular dynamics simulation is a useful tool to study the conformer distribution of IDPs. However, most generic protein force fields were found to be insufficient in simulations of IDPs. Here, we report our development for the CHARMM community. Our residue-specific IDP force field (CHARMM36IDPSFF) was developed based on the base generic force field with CMAP corrections for all 20 naturally occurring amino acids. Multiple tests show that the simulated chemical shifts with the newly developed force field are in quantitative agreement with NMR experiment and are more accurate than the base generic force field. Comparison of J-couplings with previous work shows that CHARMM36IDPSFF and its corresponding base generic force field have their own advantages. In addition, CHARMM36IDPSFF simulations also agree with experiment for SAXS profiles and radii of gyration of IDPs. Detailed analysis shows that CHARMM36IDPSFF can sample more diverse and disordered conformers. These findings confirm that the newly developed force field can improve the balance of accuracy and efficiency for the conformer sampling of IDPs.

The LaNiO3 nanoparticles were prepared by a sol-gel process. The LaNiO3 nanoparticles were characterized by powder X-ray diffraction (XRD), scanning electron microscopy (SEM) and UV-Vis diffuse reflectance spectroscopy (DRS). XRD and SEM demonstrate the successful synthesis of single phase perovskite LaNiO3 and an average grain size of 80 nm in diameter. It was found that the as-prepared LaNiO3 shows strong visible-light absorption with absorption onset of 545 nm, indicating a narrow optical band gap of 2.28 eV. Consequently, LaNiO3 nanoparticles show high visible-light photocatalytic activity for decomposition of methyl orange in comparison with the commercial Degussa P25. The photocatalytic experiment shows the high photocatalytic activity for the decomposition of methyl orange under visible-light irradiation, which is attributed to the strong visible-light absorption.

The LaFeO3 nanoparticle was synthesized using Fe(NO3)3 and La(NO3)3 as starting materials by homogeneous precipitation method. The as-prepared LaFeO3 product was characterized by powder X-ray diffraction (XRD), scanning electron microscopy (SEM) and UV-visible diffuse reflectance spectroscopy (DRS). XRD and SEM demonstrate the successful synthesis of single phase perovskite LaFeO3 and with 60-80 nm particle size. It was found that the as-prepared LaFeO3 shows strong visible-light absorption with absorption onset of 532 nm, indicating a narrow optical band gap of 2.33 eV. Furthermore, the as-prepared LaFeO3 shows high visible-light photocatalytic activity for decomposition of methylene blue in comparison with the commercial Degussa P25.

The binding modes of a group of Factor Xa (fXa) inhibitors were studied using FlexX. CoMFA, CoMSIA, HQSAR and SVM models for inhibition potency were constructed with the conformers obtained from the molecular docking. 3D-QSAR models for oral biovailability were also constructed with the subset inhibitors. The results show that these models possess good prediction ability. The influence of substituents for the activity and oral bioavailability were explored by comparing the constructed 3D-QSAR models. We found that some substituents have consistent effects on inhibition potency and oral bioavailablity, but some have inconsistent effects. We observed equally that the different methods involved in this study, such as molecular docking, SVM, HQSAR and 3D-QSAR models, could be used not only for the prediction, but they are also complementary each to other. They are helpful for better understanding the interaction mechanism between inhibitors and fXa receptor.

No abstract