Accurate Identification of Human Phosphorylated Proteins by Ensembling Supervised Kernel Self-organizing Maps.

Protein phosphorylation is a vital physiological process, which plays a critical role in controlling survival differentiation, cell growth, metabolism and apoptosis. The accurate identification of whether a protein will be phosphorylated solely from protein sequence is especially useful for both basic research and drug development. In this study, a new predictor specifically designed for the prediction of human phosphorylated proteins is proposed. The proposed method first train two supervised kernel self-organizing maps (SKSOMs): one is trained with feature from protein physiochemical composition view, while the other is trained with feature from protein evolutionary information view. Then, the two trained SKSOMs are ensembled to perform the final prediction. Rigorous computational experiments show that the proposed method achieves 78.75 % and 0.561 on ACC and MCC, which are 6.96 % and 12.5 % higher than that of the state-of-the-art predictor. Overall, the study demonstrated a new sensitive avenue to identify human phosphorylated proteins and could be readily extended to recognize phosphorylated proteins for other species.

Highly Selective, ppb-Level Xylene Gas Detection by Sn2+-Doped NiO Flower-Like Microspheres Prepared by a One-Step Hydrothermal Method.

Detecting xylene gas is an important means of avoiding human harm from gas poisoning. A precise measurement demands that the gas sensor used must have high sensitivity, high selectivity, and low working temperature. To meet these requirements, in this study, Sn2+-doped NiO flower-like microspheres (SNM) with different amounts of Sn2+ synthesized by a one-step hydrothermal process were investigated. The responses of gas sensors based on different Sn2+-doped NiO materials for various targeting gases were fully characterized. It was found that all of the synthesized materials exhibited the best gas response at a working temperature of 180 degrees, which was much lower than the previously reported working temperature range of 300-500 degrees. When exposed to 10 ppm xylene, the 8 at% Sn2+-doped NiO sensor (mol ratio) exhibited the highest response, with a value of 30 (Rg/Ra). More significantly, the detection limit of the 8 at% Sn2+-doped NiO sensor for xylene is down in the ppb level. The Sn2+-doped NiO material also exhibits excellent selectivity for other gases with long-term stability and repeatability. The significant improvement in the response to xylene can theoretically be attributed to a decrease in the intrinsic hole carrier concentration, higher amounts of adsorbed oxygen and active sites.

Physical origin underlying the prenucleation-cluster-mediated nonclassical nucleation pathways for calcium phosphate.

The involvement of prenucleation clusters (PNCs) in crystallization from a supersaturated solution has been recently admitted within the framework of nonclassical nucleation theory; however, little is known about PNCs, at the quantitative level, for their formation mechanism and stability, the new phase formed by them, as well as their impact on nucleation barriers. Herein, using the sophisticated free energy calculations with a cumulative simulation time of over 5 µs, we identify a thermodynamically favored pathway of the PNC-mediated nucleation for calcium phosphate, starting with the ion pair association in solution. We demonstrate that such an ion association occurs not only between cations and anions, but also for the polyatomic species with charges of the same sign, which, in fact, leads to PNC formation via the consecutive coordination of the phosphate ions to calcium. The free energy decomposition calculations illustrate that the water phase is capable to either hinder or promote ion association for the abovementioned processes, and its specific role is intricately related to the characteristics of the hydration shell around calcium ions. The favorable interactions between the highly charged species play a crucial role in stabilizing the PNC complexes and the aggregates formed by PNCs. Furthermore, our present work reveals that the uptake of an extra calcium ion is the first and mandatory step to trigger PNC aggregation into amorphous calcium phosphate (ACP) by eliminating the related free energy barriers. Our theoretical study successfully provides quantitative explanations to a large set of experimental data in the field, which is currently under intense discussions associated with the nonclassical nucleation mechanism. The combination of computational methods developed in our present work offers a feasible and general solution to quantitatively and systematically study ion associations and crystal nucleation/growth in an aqueous solution at the atomic level, which are normally inaccessible to most of the existing experimental acquisitions.

Quantitatively Identifying the Roles of Interfacial Water and Solid Surface in Governing Peptide Adsorption.

Understanding the molecular mechanism of protein adsorption on solids is critical to their applications in materials synthesis and tissue engineering. Although the water phase at the surface/water interface has been recognized as three types: bulk water, intermediate water phase and surface-bound water layers, the roles of the water and surface in determining the protein adsorption are not clearly identified, particularly at the quantitative level. Herein, we provide a methodology involving the combination of microsecond strengthen sampling simulation and force integration to quantitatively characterize the water-induced contribution and the peptide-surface interactions into the adsorption free energy. Using hydroxyapatite and graphene surfaces as examples, we demonstrate how the distinct interfacial features dominate the delicate force balance between these two thermodynamics parameters, leading to surface preference/resistance to peptide adsorption. Specifically, the water layer provides sustained repelling force against peptide adsorption, as indicated by a monotonic increase in the water-induced free energy profile, whereas the contribution from the surface-peptide interactions is thermodynamically favorable to peptide adsorptions. More importantly, the revealed adsorption mechanism is critically dictated by the distribution of water phase, which plays a crucial role in establishing the force balance between the interactions of the peptide with the water layer and the surface. For the HAP surface, the charged peptide exhibits strong binding affinity to the surface, due to the controlling contribution of peptide-surface interaction in the intermediate water phase. The surface-bound water layers are observed as the origin of bioresistance of solid surfaces toward the adsorption of charge-neutral peptides. The preferred peptide adsorption on the graphene, however, is dominated by the surface-induced component at the water layers adjacent to the surface. Our results further elucidate that the intermediate water phase significantly shortens the effective range of the surface dispersion force, in contrast to the observation on the hydrophilic surface.

Method Evaluations for Adsorption Free Energy Calculations at the Solid/Water Interface through Metadynamics, Umbrella Sampling, and Jarzynski's Equality.

Considerable interest in characterizing protein/peptide-surface interactions has prompted extensive computational studies on calculations of adsorption free energy. However, in many cases, each individual study has focused on the application of free energy calculations to a specific system; therefore, it is difficult to combine the results into a general picture for choosing an appropriate strategy for the system of interest. Herein, three well-established computational algorithms are systemically compared and evaluated to compute the adsorption free energy of small molecules on two representative surfaces. The results clearly demonstrate that the characteristics of studied interfacial systems have crucial effects on the accuracy and efficiency of the adsorption free energy calculations. For the hydrophobic surface, steered molecular dynamics exhibits the highest efficiency, which appears to be a favorable method of choice for enhanced sampling simulations. However, for the charged surface, only the umbrella sampling method has the ability to accurately explore the adsorption free energy surface. The affinity of the water layer to the surface significantly affects the performance of free energy calculation methods, especially at the region close to the surface. Therefore, a general principle of how to discriminate between methodological and sampling issues based on the interfacial characteristics of the system under investigation is proposed.