In this work, the adsorptions of hydrophobin (HFBI) on four different self-assembled monolayers (SAMs) (i.e., CH3-SAM, OH-SAM, COOH-SAM, and NH2-SAM) were investigated by parallel tempering Monte Carlo and molecular dynamics simulations. Simulation results indicate that the orientation of HFBI adsorbed on neutral surfaces is dominated by a hydrophobic dipole. HFBI adsorbs on the hydrophobic CH3-SAM through its hydrophobic patch and adopts a nearly vertical hydrophobic dipole relative to the surface, while it is nearly horizontal when adsorbed on the hydrophilic OH-SAM. For charged SAM surfaces, HFBI adopts a nearly vertical electric dipole relative to the surface. HFBI has the narrowest orientation distribution on the CH3-SAM, and thus can form an ordered monolayer and reverse the wettability of the surface. For HFBI adsorption on charged SAMs, the adsorption strength weakens as the surface charge density increases. Compared with those on other SAMs, a larger area of the hydrophobic patch is exposed to the solution when HFBI adsorbs on the NH2-SAM. This leads to an increase of the hydrophobicity of the surface, which is consistent with the experimental results. The binding of HFBI to the CH3-SAM is mainly through hydrophobic interactions, while it is mediated through a hydration water layer near the surface for the OH-SAM. For the charged SAM surfaces, the adsorption is mainly induced by electrostatic interactions between the charged surfaces and the oppositely charged residues. The effect of a hydrophobic dipole on protein adsorption onto hydrophobic surfaces is similar to that of an electric dipole for charged surfaces. Therefore, the hydrophobic dipole may be applied to predict the probable orientations of protein adsorbed on hydrophobic surfaces.

Candida antarctica lipase B (CalB) is an efficient biocatalyst for hydrolysis and esterification, which plays an important role in the production of biodiesel in the bioenergy industries. The ordered immobilisation of lipases on different supports would be significant for its enzymatic catalysis in some biodiesel production processes; however, the underlying mechanisms and the preferred lipase orientation are not well understood yet. In this work, a fundamental understanding of the orientation and adsorption mechanism of lipase on four different nanomaterial surfaces with different surface chemistry are explored in detail by a combination of parallel tempering Monte Carlo (PTMC) and molecular dynamics (MD) simulations. Simulation results show that lipase is strongly adsorbed onto the hydrophobic graphite surface, as reflected by the large contact area and interaction energy; while the adsorption onto the hydrophilic TiO2 surface is weak due to two strongly adhered water layers; meanwhile lipase undergoes desorption and reorientation processes. For CalB adsorption on positively and negatively charged surfaces (NH2-SAM and COOH-SAM), the orientation distributions of lipase are narrow, and opposite orientations are obtained. CalB adsorbed on NH2-SAM has its catalytic centre oriented towards the surface, which is not conducive to the substrate binding; while the catalytic centre faces toward the solution when it is adsorbed on the COOH-SAM. Besides, the native structures of CalB adsorbed on different surfaces are preserved, which indicates lipase as a robust enzyme. The simulation results will promote our understanding on how surface properties of nanomaterials, such as charge or hydrophobicity, will affect lipase immobilisation, and help us in the rational design and development of immobilised lipase carriers.

A computational study is reported to high-throughput screen 137953 MOFs for a single-step membrane separation of a CO2/N2/CH4 mixture.

Crystal structure prediction (CSP) calculations can reduce risk and improve efficiency during drug development. Traditionally, CSP calculations use lattice energies computed through density functional theory. While this approach is often successful in predicting the low energy structures, it neglects the crucial role of thermal effects on polymorph stabilities. In the present study, we develop a robust and efficient protocol for predicting the relative stability of polymorphs at different temperatures. The protocol is executed on a highly parallel cloud computing infrastructure to produce results at time scales useful for drug development timelines. We demonstrate this protocol on molecule XXIII from the sixth crystal structure prediction blind test. Our results predict that Form D is the most stable experimentally observed polymorph at ambient temperature and Form C is the most stable at low temperature consistent with experiments also conducted in the present study.

In this work, the interactions between surface-functionalized gold nanoparticles (AuNPs) and asymmetric membranes and the associated cytotoxicity were explored by coarse-grained molecular dynamics simulations. Simulation results show that the surface chemistry of AuNPs and the asymmetry of lipid membranes play significant roles. AuNPs with different signs of charges spontaneously adhere to the membrane surface or penetrate the membrane core. Also, the asymmetric distribution of charged lipids in membranes can facilitate the penetration of cationic AuNPs. Increasing the surface charge density (SCD) of AuNPs can not only improve the penetration efficiency but also lead to more disruption of the membrane structure. Moreover, the flip-flop of charged lipids in the inner leaflet can be observed during the translocation of AuNPs with a high SCD. The breakdown of membrane asymmetry may hinder the cellular internalization of AuNPs in a direct penetration mechanism. More importantly, we demonstrate that the hydrophobic contact between protruding solvent-exposed lipid tails and the hydrophobic moieties of ligands can mediate the insertion of AuNPs with a low SCD into cell membranes, which will exhibit less cytotoxicity in most in vivo applications. This may open a new exciting avenue to developing nanocarriers with a higher translocation efficiency and a lower toxicity simultaneously for biomedical applications.

Free energy perturbation (FEP) has become widely used in drug discovery programs for binding affinity prediction between candidate compounds and their biological targets. However, limitations of FEP applications also exist, including, but not limited to, high cost, long waiting time, limited scalability, and breadth of application scenarios. To overcome these problems, we have developed XFEP, a scalable cloud computing platform for both relative and absolute free energy predictions using optimized simulation protocols. XFEP enables large-scale FEP calculations in a more efficient, scalable, and affordable way, for example, the evaluation of 5000 compounds can be performed in 1 week using 50–100 GPUs with a computing cost roughly equivalent to the cost for the synthesis of only one new compound. By combining these capabilities with artificial intelligence techniques for goal-directed molecule generation and evaluation, new opportunities can be explored for FEP applications in the drug discovery stages of hit identification, hit-to-lead, and lead optimization based not only on structure exploitation within the given chemical series but also including evaluation and comparison of completely unrelated molecules during structure exploration in a larger chemical space. XFEP provides the basis for scalable FEP applications to become more widely used in drug discovery projects and to speed up the drug discovery process from hit identification to preclinical candidate compound nomination.

Selective laser sintering (SLS) is an additive manufacturing technology which has shown great advantages in direct formation of the polymer, metal and their composites. However, ceramic parts prepared by the SLS still exhibit some fatal defects, including low density and poor mechanical properties. In this respect, recent advances for preparing ceramics have improved the final density and performance by adopting post-processing methods. In this review, three commonly used powder preparation approaches (i.e. mechanical mixing, solvent evaporation and dissolution-precipitation process) and two powder sintering mechanisms for the SLS are introduced. Porous ceramic parts are prepared directly through the SLS by virtue of their high porosity. And dense, high-performance Al 2 O 3 , ZrO 2 , kaolin and SiC ceramic parts with complex shape are prepared by introducing CIP technology into the SLS, indicating that the hybrid technology could be the promising route for preparing highperformance ceramic parts used in various fields.

Experimental studies have shown that the adsorption of horse heart Cytochrome c (Cyt-c) on a bare gold surface leads to the hindrance of electron transfer (ET).The underlying mechanism remains controversial. In this work, the adsorption orientation and conformation of Cyt-c on Au (111) surface were investigated by performing Monte Carlo and molecular dynamics simulations. The results show that the most favorable binding mode of Cyt-c to gold agrees with the results characterized by SEIRA spectroscopy. The adsorption is mainly contributed by the strong van der Waals interactions between the surface and residues that have long side chains, which leads to the helix A and Ω1 loop of Cyt-c being in contact with the surface and most of the α-helixes being nearly parallel to the surface. The native structure of Cyt-c is well preserved during the adsorption and only the flexible Ω1 loop and the N-terminal show a relatively larger mobility. The hindrance of ET is ascribed to the confined rotation of the heme prosthetic group and the farther positioning of the central iron to the surface (about 12.9 Å). group was near and almost vertical to the negatively charged surface while far away from the positively charged surface. 17 However, Cyt-c had a random or relatively flat orientation on the bare gold nanohole surface. 17 Lin et al. 15 probed the adsorption of Cyt-c on a bare gold surface by surface-enhanced infrared absorption (SEIRA) spectroscopy. The results showed that Cyt-c kept its native structure when adsorbed on the bare gold, with most of the α-helixes running parallel to the surface. 15 They ascribed the hindrance of ET to the adsorption orientation and suppressed rotation of the adsorbed Cyt-c. However, the adsorption orientations of Cyt-c on bare gold surface characterized by SERS and SEIRA are quite different. What is the cause of the hindrance of ET? Although some experiments can provide structural, electronic and dynamic information simultaneously, in situ detection of the orientation and conformation changes of proteins emerging at the molecular level is still technically challenging. 15 Molecular simulations are very suitable to study the behavior of protein adsorption on surfaces at the molecular level. 18 So far, a few molecular dynamics (MD) simulation studies of Cyt-c adsorption on solid surfaces have been reported. 18-25 Zhou et al. 18 studied the adsorption of Cyt-c on carboxyl-terminated SAMs (COOH-SAM) by performing Monte Carlo and MD simulations. They showed that the heme ring was near and almost vertical to the COOH-SAM surface. 18 Alvarez-Paggi et al. 21-23 employed MD simulations and electron pathway analyses to investigate the ET properties of Cyt-c adsorbed on gold functionalized by COOH-SAM. Their findings demonstrated that the ET between the adsorbed Cyt-c and the electrode was determined by the interplay between protein dynamics and tunneling probabilities. 21 Hung et al. 24 investigated the adsorption of Cyt-c on monolayer-protected metal nanoparticles (MPMNs) through a combinedIn this wor...