Search

Searching for materials with high figure of merit (ZT) has always been the goal of scientific researchers in energy field. In this paper, Tl3XSe4 crystals are found to be potential thermoelectric materials with the ZT values of 6–10 at 700 K.

The paper reports a strategy to synthesize Cd

An effective four-dimensional (4D) ab initio potential energy surface (PES) for Xe–CS2 which explicitly involves the intramolecular Q1 symmetric stretching and Q3 antisymmetric stretching vibrational coordinates of CS2 is constructed. The computations are carried out employing single- and double-excitation coupled-cluster theory with a non-iterative perturbation treatment of triple excitations [CCSD(T)] method with a large basis set. Two vibrationally averaged potentials at the ground and ν1 + ν3 (ν1 = 1, ν3 = 1) excited states are obtained by integrating the 4D potentials over the Q1 and Q3 coordinates. The potentials have a T-shaped global minimum and two equivalent linear local minima. The radial discrete variable representation/angular finite basis representation and the Lanczos algorithm are employed to calculate the rovibrational energy levels for Xe–CS2. The infrared band origin shift associated with the fundamental band of CS2 is predicted, which is red-shifted by −1.996 cm−1 in the ν1 + ν3 region. In addition, we further predict the spectroscopic parameters for the ground and the ν1 + ν3 excited states of Xe–CS2. Compared with the previous Rg–CS2 (Rg = He, Ne, Ar, Kr) complexes, we found that the complexes of the rare gas atoms with CS2 display obvious regularities.

Prostate cancer (PRAD) is a major cause of cancer-related deaths. Current monotherapies show limited efficacy due to often rapidly emerging resistance. Combination therapies could provide an alternative solution to address this problem with enhanced therapeutic effect, reduced cytotoxicity, and delayed the appearance of drug resistance. However, it is prohibitively cost and labor-intensive for the experimental approaches to pick out synergistic combinations from the millions of possibilities. Thus, it is highly desired to explore other efficient strategies to assist experimental researches. Inspired by the challenge, we construct the transcriptomics-based and network-based prediction models to quickly screen the potential drug combination for Prostate cancer, and further assess their performance by in vitro assays. The transcriptomics-based method screens nine possible combinations. However, the network-based method gives discrepancies for at least three drug pairs. Further experimental results indicate the dose-dependent effects of the three docetaxel-containing combinations, and confirm the synergistic effects of the other six combinations predicted by the transcriptomics-based model. For the network-based predictions, in vitro tests give opposite results to the two combinations (i.e. mitoxantrone-cyproheptadine and cabazitaxel-cyproheptadine). Namely, the transcriptomics-based method outperforms the network-based one for the specific disease like Prostate cancer, which provide guideline for selection of the computational methods in the drug combination screening. More importantly, six combinations (the three mitoxantrone-containing and the three cabazitaxel-containing combinations) are found to be promising candidates to synergistically conquer Prostate cancer.

An effective four-dimensional (4D)

Glucagon-like peptide-1 receptor (GLP-1R), as a member of the class B G protein-coupled receptors (GPCRs), plays a crucial role in regulating blood glucose level signal recognition through its activation. The conformation changes during the activation pathway are of particular importance for its function. To investigate the activation mechanism of GLP-1R, the crystal structures of active and inactive forms are chosen to perform a total of 2 μs of accelerated molecular dynamics (aMD) simulations and 400ns of conventional molecular dynamics (cMD) simulations. With the aid of structural analysis and potential of mean force (PMF) calculations, we reveal the role of different helices in the activation and deactivation process and obtain the intermediate states during activation and deactivation that are difficult to capture in experiments. Protein structure network (PSN) was utilised to clarify the allosteric communication pathways of activation and deactivation and reveal the mechanisms of its activation and deactivation. The results could advance our understanding of the activation mechanism of GLP-1R and the related drug design.

G-protein-coupled receptors (GPCRs) are important drug targets and generally activated by ligands. However, some experiments found that GPCRs also give rise to constitutive activity through some mutations (viz., CAM), which are usually associated with different kinds of diseases. However, the mechanisms of CAMs and their roles in interactions with drug-ligands are unclear in experiments. Herein, we used microsecond molecular dynamics simulations to study the effect of one important F282L mutation on β2AR in order to address the questions above. With the aid of principle component and correlation analysis, our results revealed that the F282L mutation could increase the instability of the overall structure, increase the dramatic fluctuations of NPxxY and extracellular loops, and decrease restraint of the helices through weakening interhelical H-bonding and correlations between residues, which could partly contribute to the constitutive activity reported by the experiments. The observations from the protein structure network (PSN) analysis indicate that the mutant exhibits less information flow than the wild β2AR and weakens the role of TM5 and TM6 in the signal transmission, but it enhances the impact of TM3 on the orthosteric pathway and TM4 on the allosteric one. In addition, the results from the virtual screening reveal that the mutant prefers to select agonists rather than antagonists, similar to the active state but opposite of the inactive state, further confirming that the F282L mutation advances the activation of β2AR. Our observations provide valuable information for understanding the mechanism of the mutation-caused constitutive activity of GPCR and related drug-design.

G protein coupled receptors (GPCRs) play a crucial role in regulating signal recognition and transduction through their activation. The conformation transition in the activation pathway is of particular importance for their function. However, it has been poorly elucidated due to experimental difficulties in determining the conformations and the time limitation of conventional molecular dynamics (CMD) simulation. Thus, in this work, we employed a targeted molecular dynamic (TMD) simulation to study the activation process from an inactive structure to a fully active one for β2 adrenergic receptor (β2AR). As a reference, 110 ns CMD simulations on wild β2AR and its D130N mutant were also carried out. TMD results show that there is at least an intermediate conformation cluster in the activation process, evidenced by the principal component analysis and the structural and dynamic differences of some important motifs. It is noteworthy that the activation of the ligand binding site lags the G-protein binding site, displaying uncoupled correlation. Comparisons between the CMD and TMD results show that the D130N mutation significantly speeds up ICL2 and key ionic lock to enter into the intermediate state, which to some extent facilitates the activation involved in the NPxxY, DRY region and the separation between TM3 and TM6. However, the contribution from the D130N mutation to the activation of the ligand binding site could not be observed within the scale of 110 ns time. These observations could provide novel insights into previous studies for better understanding of the activation mechanism for β2AR.

Correction for ‘Theoretical calculation of a full-dimensional ab initio potential energy surface and prediction of infrared spectra for Xe–CS2’ by Miao Qin et al., RSC Adv., 2019, 9, 20925–20930.

Thrombin-binding aptamer (TBA) with the sequence 5′GGTTGGTGTGGTTGG3′ could fold into G-quadruplex, which correlates with functionally important genomic regionsis. However, unfolding mechanism involved in the structural stability of G-quadruplex has not been satisfactorily elucidated on experiments so far. Herein, we studied the unfolding pathway of TBA by a combination of molecular dynamics simulation (MD) and Markov State Model (MSM). Our results revealed that the unfolding of TBA is not a simple two-state process but proceeds along multiple pathways with multistate intermediates. One high flux confirms some observations from NMR experiment. Another high flux exhibits a different and simpler unfolding pathway with less intermediates. Two important intermediate states were identified. One is similar to the G-triplex reported in the folding of G-quadruplex, but lack of H-bonding between guanines in the upper plane. More importantly, another intermediate state acting as a connector to link the folding region and the unfolding one, was the first time identified, which exhibits higher population and stability than the G-triplex-like intermediate. These results will provide valuable information for extending our understanding the folding landscape of G-quadruplex formation.

Compared with para-substitution, substituent effects ( R = NH 2, OH , CH 3, F , Cl , H , SiH 3, CHO , CN , NO 2) of meta-position effects on hydrogen-bonded complex of aniline with one water molecule are studied at B3LYP/6-311++G(d,p) level of theory. The differences in hydrogen bonding and some properties associated with the H -bond (such as bond length, vibrational frequency, binding energies, p K a values of aniline derivatives) are discussed between meta and para substitutions. Natural bond orbital (NBO) and atoms in molecules (AIM) analysis are applied to investigate the physical origin of the differences. The results show that the differences are mainly attributed to the variations in electron delocalization from amino group to phenyl ring (reflected by [Formula: see text] interaction) induced by substituents.

Substituent effects (R = F, OH, OCF 3 , OCH 3 , CN, CHO, NH 2 , NO, CH 3 , CF 3 , PH 2 , SH, SiH 3 ) on C-substituted methanimine were investigated using B3LYP and G3 calculations. The physical origin of substituent effects is explored by means of NBO (nature bond orbital) and AIM (atoms in molecules) as well as correlation analysis. The results reveal that the π -withdrawing/donating ability of substituents plays a dominant role in influencing the atomic charge on the C N nitrogen while the charge variation on the C N carbon atom attached by substituents can be well described by the substituent group electronegativity. AIM analysis indicates that the substituent changes the atomic charge adjacent to it through the modification of its interatomic surfaces. In terms of NBO analysis, the effect of substituents on the trans/cis inversion barriers can be attributed to the substitution induced variations on hyperconjugation of lone pair on the inverting nitrogen ( n N ) into the adjacent σ ∗(C R) orbital in the transition state, and displays a strong dependence on the electronegativity of substituent groups. The isodesmic reaction suggests that the highly electronegative substituents along with strong π -donating character would obviously stabilize the C-substituted imines.

Amino acid network is the reduced representation of protein structure, which benefits the investigation of protein structure. And network paradigm offers an insight into viewing global connectivity of protein and studying the interaction between secondary structures by visualizing amino acid networks. However, there exists some disadvantages in current research. Much research about protein structures are based on protein contact map, but it cannot provide an easy way to present the local regularity and the topology of protein structures. Until current research recently consider primary structure of protein cause small-world property of amino acid network and neglect the effects of secondary structures. In this paper, we present two algorithms RandomSS and RandomSC, and compare them with RandomNN algorithm. We find not only primary structures but also secondary structures play key roles in emergence of small-world property in amino acid network. The secondary structure of protein in amino acid network is regular, and the inherent regularity reinforces small-world property. Moreover, in order to reveal the characteristic patterns of the topology of protein structures and visualize the regular layout of Helix and Sheet structures and the interaction between secondary structures, we use network visualization methods to show amino acid networks. And amino acid network is visualized by macroscopic view and microscopic view to show different regions of protein, which own various roles. This paper also provides a new view to study protein structure by network paradigm.

The enzyme immobilization has been adopted to enhance the activity and stability of enzymes in non-aqueous enzymatic catalysis. However, the activation and stabilization mechanism has been poorly understood on experiments. Thus, we used molecular dynamics simulation to study the adsorption of α-chymotrypsin (α-ChT) on carbon nanotube (CNT) in aqueous solution and heptane media. The results indicate that α-ChT has stronger affinity with CNT in aqueous solution than in heptane media, as confirmed by more adsorption atoms, larger contact area and higher binding free energies. Although the immobilization causes significant structure deviations from the crystal one, no significant changes in secondary structure of the enzyme upon adsorption are observed in the two media. Different from aqueous solution, the stabilization effects on some local regions far from the surface of CNT were observed in heptane media, in particular for S1 pocket, which should contribute to the preservation of specificity reported by experiments. Also, CNT displays to some extent stabilization role in retaining the catalytic H-bond network of the active site in heptane media, which should be associated with the enhanced activity of enzymes. The observations from the work can provide valuable information for improving the catalytic properties of enzymes in non-aqueous media.

The use of enzymes in nonaqueous solvent has been one of the most exciting facets of enzymology in recent times; however, the mechanism of how organic solvent and essential water influence on structure and function of enzyme has been not satisfactorily explained in experiments, which limit its further application. Herein, we used molecular dynamics (MD) simulation to study γ-chymotrypsin in two types of media (viz., acetonitrile media with inclusion of 151 crystal water molecules and aqueous solution). On the basis of the MD result, the truncated active site modes containing two specific solvent molecules are furthered studied at the B3LYP/6-31+G(d,p) level of theory within the framework of PCM model. The results show that the acetontrile solvent gives rise to an extent deviation of enzyme structure from the native one, a drop in the flexibility and the total SASA of enzyme. The QM study further reveals that the structure variation of the active pocket caused by acetonitrile would lead to a weakened strength in the catalytic H-bond network, a drop in the pK(a) value of His57, and an increase in the proton transfer barriers from the Ser195 to the His57 residue, which may contribute to the drop in the enzymatic activity in acetontrile media. In addition, the crystal waters play an importance role in retaining the catalytic H-bond network and weakening the acetonitrile-induced variations above, which may be associated with the fact that the enzyme could retain catalytic activity in microhydration acetonitrile media.

This work mainly studies the effects of the position (there are two possible hydrated sites) and the manner (i.e., whether water acts as a proton donor or acceptor) of hydration by various numbers of water molecules on the stability of 14 solvated N-methylacetamide structures, NMA-(H(2)O)( n ) (n = 1-3), as well as the binding strength between the NMA and the water cluster, using molecular dynamics (MD) and B3LYP methods. Natural bond orbital (NBO) analysis is used to explore the origin of these effects. Some novel observations are obtained from the work. Our results show that monohydration at the carbonyl site favors stability and binding strength compared to monohydration at the amino site. Similarly, the preferred hydration at the carbonyl site is observed for dihydrated NMAs when the second water is added as a proton donor to the C=O group or the first water is H-bonded to the C=O group. However, unfavorable hydration at the C=O site occurs if the second water acts as a proton acceptor. Trihydration by a ring cluster of three water molecules at either the carbonyl site or the amino one yields relatively stable complexes, but significantly disfavors binding strength. The other trihydrated NMAs show similar behavior to dihydrated NMAs. In addition, our results show that the C=O and N-H frequencies can still be utilized to examine the H-bond effects of the water cluster.