Journal of molecular graphics & modelling最新文献

SIRT6 is of interest for its promising effect in the treatment of aging-related diseases. Studies have shown quercetin (QUE) and its derivatives have varying degrees of effect on the catalytic effect of SIRT6. In the research, the effect of QUE on the protein-substrate interaction in the SIRT6-mediated mono-ADP ribosylation system was investigated by conventional molecular dynamics (MD) simulations combined with MM/PBSA binding free energy calculations. The results show that QUE can bind stably to SIRT6 with the binding energy of −22.8 kcal/mol and further affect the atomic interaction between SIRT6 and NAD⁺ (or H3K9), resulting in an increased affinity between SIRT6-NAD⁺ and decreased SIRT6-H3K9 binding capacity. At the same time, the binding of QUE can also alter some structural characteristics of the protein, with large shifts occurring in the residue regions involving the N-terminal (residues 1–27), Rossmann fold regions (residues 55–92), and ZBD (residues 164–179). Thus, QUE shows great potential as a scaffold for the design of novel potent SIRT6 modulators.

This study delves into the prediction of protein-peptide interactions using advanced machine learning techniques, comparing models such as sequence-based, standard CNNs, and traditional classifiers. Leveraging pre-trained language models and multi-view window scanning CNNs, our approach yields significant improvements, with ProtTrans standing out based on 2.1 billion protein sequences and 393 billion amino acids. The integrated model demonstrates remarkable performance, achieving an AUC of 0.856 and 0.823 on the PepBCL Set_1 and Set_2 datasets, respectively. Additionally, it attains a Precision of 0.564 in PepBCL Set 1 and 0.527 in PepBCL Set 2, surpassing the performance of previous methods. Beyond this, we explore the application of this model in cancer therapy, particularly in identifying peptide interactions for selective targeting of cancer cells, and other fields. The findings of this study contribute to bioinformatics, providing valuable insights for drug discovery and therapeutic development.

Water is an indispensable material for human life. Unfortunately, the development of industrial activities has reduced the quality of water resources in the world. Meantime, heavy metals are an important factor in water pollution due to their toxicity. This study highlights the method for the capture of heavy metal ions from wastewater using the procedure of adsorption. The adsorption of toxic heavy metal ions (Pb²⁺, Hg²⁺, and Cd²⁺) on Ca₂C as well as Cr₂C carbide-nitride MXene monolayers is investigated using the density functional theory. We have carried out the optimization of the considered MXenes by nine DFT functionals: PBE, TPSS, BP86, B3LYP, TPSSh, PBE0, CAM-B3LYP, M11, and LC-WPBE. Our results have shown a good agreement with previously measured electronic properties of the Ca₂C and Cr₂C MXene layers and the PBE DFT method. The calculated cohesive energy for the Ca₂C and Cr₂C MXene monolayers are −4.12 eV and −4.20 eV, respectively, which are in agreement with the previous studies. The results reveal that the adsorbed heavy metal ions have a substantial effect on the electronic properties of the considered MXene monolayers. Besides, our calculations show that the metal/MXene structures with higher electron transport rates display higher binding energy as well as charge transfers between the metal and Ca₂C and Cr₂C layers. Time-dependent density functional analysis also displayed “ligand to metal charge transfer” excitations for the metal/MXene systems. The larger Ebin for the Pb@Ca₂C as well as Pb@Cr₂C are according to larger redshifts which are expected (Δλ = 45 nm and 71 nm, respectively). Our results might be helpful for future research toward the application of carbide-nitride MXene materials for removing wastewater pollutants.

In this paper, we have performed an all-atom molecular dynamics simulation to understand the structure and dynamics of Na⁺ ions in water mixed Ionic liquids (Water in Ionic liquid). Two ionic liquid (IL) systems consist of (1) 1-butyl-3-methylimidazolium [BMIM] tetrafluoroborate [BF₄] and (2) 1-butyl-3-methylimidazolium [BMIM] hexafluorophosphate [PF₆] were considered in this work. We understand various inter^-molecular structures and dynamic and thermodynamic behaviours of Na⁺ ions in the water^-mixed IL systems. The water (H₂O) mole fractions (x) varied from 0.33 to 0.71. The neat ILs [BMIM][BF₄] and [BMIM][PF₆] pairwise radial distribution functions show a decrease with an increase in x. The [BMIM][PF₆] exhibits a strong coordination structure with Na⁺ ions across the entire range of x values. The rdf between the pairs of Na⁺-[PF₆] presents a significant interaction compared to Na⁺ and [BF₄]. The Na ⁺ ions manifested greater coordination with H₂O In H₂O-[BMIM][PF₆] compared to H₂O-[BMIM][BF₄]. The self-diffusion coefficient (D) values of Na ⁺ ions increase with the rise in x in both ILs. The D values of Na ⁺ ions are 10-fold higher in [BMIM][BF₄] than [BMIM][PF₆]. The ionic conductivity values are higher for [BMIM][BF₄]. Overall, this paper unveils molecular-level insights for understanding the behavior of Na⁺ ions in the water in ionic liquid systems.

H₂S is a highly toxic, flammable gas that poses risks to health, the environment, and industrial infrastructure. Zeolites, with their high porosity, offer a promising solution for its removal. This study employs density functional theory (DFT) to investigate the adsorption behavior of H₂S within the Li-ABW zeolite framework, focusing on the synergistic effect of co-adsorbed water molecules. Six distinct systems were modeled: empty Li-ABW zeolite, half and full filled Li-ABW with H₂O or H₂S molecules, and equally filled zeolite with H₂S and H₂O molecules. Detailed analysis of geometric, energetic, and electronic properties reveals that the presence of water significantly enhances H₂S adsorption in Li-ABW. Increased bond lengths between H₂S and the zeolite framework suggest possible dissociative adsorption, while weakened H₂S-zeolite interaction compared to H₂O-zeolite interaction indicates facile H₂S desorption. Furthermore, charge transfer analysis and HOMO/LUMO plots highlight stronger interactions and a more balanced electron distribution in the co-adsorbed system. Interestingly, the presence of water minimizes structural deformations of the zeolite framework while facilitating the formation of additional hydrogen bonds, potentially further promoting H₂S desorption through water extraction. These findings demonstrate that Li-ABW zeolite, particularly in conjunction with water molecules, exhibits remarkable potential for efficient and selective H₂S adsorption, offering promising avenues for practical applications in gas sweetening and industrial gas purification. In order to realize this potential, further investigation into the effects of solvents and cation exchange is necessary, which are outlined for future research.

Bruton tyrosine kinases (BTKs) play critical roles in various diseases, including chronic lymphatic leukemia (CLL), Waldenström Macroglobulinemia, Marginal Zone Lymphoma, Mantle Cell Lymphoma (MCL), and Graft Versus Host diseases. BTKs are a family of tyrosine kinases involved in B lymphocyte signal transduction, development, and maturation. Their overexpression can lead to cancer as they are essential for the activation of the B Cell Receptor (BCR) signaling pathway. Blocking the activation of BTKs presents a promising approach for treating CLL. This study was centered around the identification of small-molecule therapeutics that have an impact on human BTK. The covalently bound Ibrutinib molecule, recognized for its ability to inhibit BTK, was used as the query molecule. IUPAC text files containing molecular fragments of Ibrutinib were employed to virtually screen five different libraries comprising small-molecules, resulting in the screening of over 2.4 million synthesized compounds. Covalent docking simulations were applied to the selected small-molecules obtained through text mining from databases. Potent hit molecules capable of inhibiting BTKs through virtual screening algorithms were identified, paving the way for novel therapeutic strategies in the treatment of CLL.

STING (stimulator of interferon genes) is a crucial protein in the innate immune system's response to viral and bacterial infections. In this study, we investigated the mechanistic and energetic mechanism of the conformational transition process of STING activated by cGAMP binding. We found that the STING connector region undergoes an energetically unfavorable rotation during this process, which is compensated by the favorable interaction between cGAMP and the STING ligand binding domain. We further studied several disease-causing mutations and found that the V155 M mutation facilitates a smoother transition in the STING connector region. However, the V147L mutation exhibits unfavorable conformational transition energy, suggesting it may hinder STING activation pathway that relies on connector region rotation. Despite being labeled as hyperactive, the widespread prevalence of V147L/V147I mutations across species implies a neutral character, indicating complexity in its role. Overall, our analysis deepens the understanding of STING activation within the connector region, and targeting this region with compounds may provide an alternative approach to interfering with STING's function.

The graphene-like monolayer of carbon, boron and nitrogen that maintains the native hexagonal atomic lattice (BCN), is a novel semiconductor with special thermal properties. Herein, with the aid of a non-equilibrium molecular dynamics approach (NEMD), we study phonon thermal rectification in a hybrid system of pure graphene and BCN (G-BCN) in various configurations under a series of positive and negative temperature gradients. We begin by investigating the relation of thermal rectification to sample’s mean temperature, $T$, and the imposed temperature difference, $\Delta T$, between the two heat baths at its ends. We then move to explore the effect of varying strain levels of our sample on thermal rectification, followed by Kapitza resistance calculations at the G-BCN interface, which shed light on the interface effects on thermal rectification. Our simulation results reveal a BCN-configuration-dependent behavior of thermal rectification. Finally, the underlying mechanism leading to a preferred direction for phonons is studied using phonon density of states (DOS) on both sides of the G-BCN interface.

A new iminophosphorane-thiourea superbase was rationally designed and investigated as an organocatalyst for the enantioselective Michael addition reaction of nitromethane to 4-phenylbut-3-en-2-one. Starting from an iminophosphorane-thiourea organocatalyst structure already known, we have used theoretical calculations to determine the structures of transition states involved in the carbon-carbon bond formation step and carried out structural modifications to accelerate the reaction rate and to increase the enantioselectivity. The effective structural modification was adding a rigid hydroxyl group able to make an additional hydrogen bond to the transition state, producing a substantial decrease of the ΔG^‡ by 7 kcal mol⁻¹. The enantiomeric excess is predicted to be above of 97% using the reliable M06-2X and ωB97M − V functionals. The determination of the complete reaction mechanism and free energy profile was followed by a detailed microkinetic analysis. The present study points out a new direction for structural modifications on this kind of organocatalyst.

ADP-glucose pyrophosphorylase plays a pivotal role as an allosteric enzyme, essential for starch biosynthesis in plants. The higher plant AGPase comparises of a pair of large and a pair of small subunits to form a heterotetrameric complex. Growing evidence indicates that each subunit plays a distinct role in regulating the underlying mechanism of starch biosynthesis. In the rice genome, there are four large subunit genes (OsL1-L4) and three small subunit genes (OsS1, OsS2a, and OsS2b). While the structural assembly of cytosolic rice AGPase subunits (OsL2:OsS2b) has been elucidated, there is currently no such documented research available for plastidial rice AGPases (OsL1:OsS1). In this study, we employed protein modeling and MD simulation approaches to gain insights into the structural association of plastidial rice AGPase subunits. Our results demonstrate that the heterotetrameric association of OsL1:OsS1 is very similar to that of cytosolic OsL2:OsS2b and potato AGPase heterotetramer (StLS:StSS). Moreover, the yeast-two-hybrid results on OsL1:OsS1, which resemble StLS:StSS, suggest a differential protein assembly for OsL2:OsS2b. Thus, the regulatory and catalytic mechanisms for plastidial AGPases (OsL1:OsS1) could be different in rice culm and developing endosperm compared to those of OsL2:OsS2b, which are predominantly found in rice endosperm.