Computational design and preparation of water-compatible noncovalent imprinted microspheres.

Herein, 2,4-dichlorophenoxyacetic acid (2,4-D) was used as a model template in a rational design strategy to produce water-compatible noncovalent imprinted microspheres. The proposed approach involved computational modelling for screening functional monomers and a simple method for preparing monodisperse and highly cross-linked microspheres. The fabricated non-imprinted polymer (NIP) and 2,4-d-imprinted polymer (2,4-d-MIP) were characterised, and their adsorption capabilities in an aqueous environment were evaluated. Results reveal that the pseudo-second-order kinetics model was appropriate for representing the adsorption of 2,4-D on NIP and 2,4-d-MIP, with R2 values of 0.97 and 0.99, respectively. The amount of 2,4-D adsorbed on 2,4-d-MIP (97.75 mg g-1) was considerably higher than those of phenoxyacetic acid (35.77 mg g-1), chlorogenic acid (9.72 mg g-1), spiramycin (1.56 mg g-1) and tylosin (1.67 mg g-1). Furthermore, it exhibited strong resistance to protein adsorption in an aqueous medium. These findings confirmed the feasibility of the proposed approach, providing a reference for the development of water-compatible noncovalent imprinted polymers.

Conformational States of the GDP- and GTP-Bound HRAS Affected by A59E and K117R: An Exploration from Gaussian Accelerated Molecular Dynamics.

The HRAS protein is considered a critical target for drug development in cancers. It is vital for effective drug development to understand the effects of mutations on the binding of GTP and GDP to HRAS. We conducted Gaussian accelerated molecular dynamics (GaMD) simulations and free energy landscape (FEL) calculations to investigate the impacts of two mutations (A59E and K117R) on GTP and GDP binding and the conformational states of the switch domain. Our findings demonstrate that these mutations not only modify the flexibility of the switch domains, but also affect the correlated motions of these domains. Furthermore, the mutations significantly disrupt the dynamic behavior of the switch domains, leading to a conformational change in HRAS. Additionally, these mutations significantly impact the switch domain's interactions, including their hydrogen bonding with ligands and electrostatic interactions with magnesium ions. Since the switch domains are crucial for the binding of HRAS to effectors, any alterations in their interactions or conformational states will undoubtedly disrupt the activity of HRAS. This research provides valuable information for the design of drugs targeting HRAS.

Interaction of Asn297-Linked Glycan Ligands with the Fc Fragment of the Immunoglobulin Class G1: A Molecular Dynamics Simulation Study.

The allosteric modulation of the homodimeric H10-03-6 protein to glycan ligands L1 and L2, and the STAB19 protein to glycan ligands L3 and L4, respectively, has been studied by molecular dynamics simulations and free energy calculations. The results revealed that the STAB19 protein has a significantly higher affinity for L3 (-11.38 ± 2.32 kcal/mol) than that for L4 (-5.51 ± 1.92 kcal/mol). However, the combination of the H10-03-6 protein with glycan L2 (1.23 ± 6.19 kcal/mol) is energetically unfavorable compared with that of L1 (-13.96 ± 0.35 kcal/mol). Further, the binding of glycan ligands L3 and L4 to STAB19 would result in the significant closure of the two CH2 domains of the STAB19 conformation with the decrease of the centroid distances between the two CH2 domains compared with the H10-03-6/L1/L2 complex. The CH2 domain closure of STAB19 relates directly to the formation of new hydrogen bonds and hydrophobic interactions between the residues Ser239, Val240, Asp265, Glu293, Asn297, Thr299, Ser337, Asp376, Thr393, Pro395, and Pro396 in STAB19 and glycan ligands L3 and L4, which suggests that these key residues would contribute to the specific regulation of STAB19 to L3 and L4. In addition, the distance analysis revealed that the EF loop in the H10-03-6/L1/L2 model presents a high flexibility and partial disorder compared with the stabilized STAB19/L3/L4 complex. These results will be helpful in understanding the specific regulation through the asymmetric structural characteristics in the CH2 and CH3 domains of the H10-03-6 and STAB19 proteins.

EVLncRNAs 3.0: an updated comprehensive database for manually curated functional long non-coding RNAs validated by low-throughput experiments.

Long noncoding RNAs (lncRNAs) have emerged as crucial regulators across diverse biological processes and diseases. While high-throughput sequencing has enabled lncRNA discovery, functional characterization remains limited. The EVLncRNAs database is the first and exclusive repository for all experimentally validated functional lncRNAs from various species. After previous releases in 2018 and 2021, this update marks a major expansion through exhaustive manual curation of nearly 25 000 publications from 15 May 2020, to 15 May 2023. It incorporates substantial growth across all categories: a 154% increase in functional lncRNAs, 160% in associated diseases, 186% in lncRNA-disease associations, 235% in interactions, 138% in structures, 234% in circular RNAs, 235% in resistant lncRNAs and 4724% in exosomal lncRNAs. More importantly, it incorporated additional information include functional classifications, detailed interaction pathways, homologous lncRNAs, lncRNA locations, COVID-19, phase-separation and organoid-related lncRNAs. The web interface was substantially improved for browsing, visualization, and searching. ChatGPT was tested for information extraction and functional overview with its limitation noted. EVLncRNAs 3.0 represents the most extensive curated resource of experimentally validated functional lncRNAs and will serve as an indispensable platform for unravelling emerging lncRNA functions. The updated database is freely available at https://www.sdklab-biophysics-dzu.net/EVLncRNAs3/.

Molecular mechanism of calcitriol enhances membrane water permeability.

Helicobacter pylori (H. pylori) exhibits a unique membrane lipid composition, including dimyristoyl phosphatidylethanolamine (DMPE) and cholesterol, unlike other Gram-negative bacteria. Calcitriol has antimicrobial activity against H. pylori, but cholesterol enhances antibiotics resistance in H. pylori. This study explored the changes in membrane structure and the molecular mechanisms of cholesterol/calcitriol translocation using well-tempered metadynamics (WT-MetaD) simulations and microsecond conventional molecular dynamics (CMD) simulations. Calcitriol facilitated water transport across the membrane, while cholesterol had the opposite effect. The differing effects might result from the tail 25-hydroxyl group and a wider range of orientations of calcitriol in the DMPE/dimyristoyl phosphatidylglycerol (DMPG) (3:1) membrane. Calcitriol moves across the bilayer center without changing its orientation along the membrane Z-axis, becomes parallel to the membrane surface at the membrane-water interface, and then rotates approximately 90° in this interface. The translocation mechanism of calcitriol is quite different from the flip-flop of cholesterol. Moreover, calcitriol crossed from one layer to another more easily than cholesterol, causing successive perturbations to the hydrophobic core and increasing water permeation. These results improve our understanding of the relationship between cholesterol/calcitriol concentrations and the lipid bilayer structure and the role of lipid composition in water permeation.

Effects of C-Terminal Lys-Arg Residue of AapA1 Protein on Toxicity and Structural Mechanism.

Previous experimental investigations have established the indispensability of the C-terminal Lys-Arg residues in the toxic activity of the AapA1 toxin protein. AapA1 is classified as a type I toxin-antitoxin (TA) bacterial toxin, and the precise impact of the C-terminal Lys-Arg residues on its structure and mechanism of action remains elusive. To address this knowledge gap, the present study employed molecular dynamics (MD) and enhanced sampling Well-tempered Two-dimensional Metadynamics (2D-MetaD) simulations to examine the behavior of the C-terminal Lys-Arg residues of truncated AapA1 toxin (AapA1-28) within the inner membrane of Escherichia coli. Specifically, the study focused on the elucidation of possible conformation states of AapA1-28 protein in POPE/POPG (3:1) bilayers and their interactions between the protein and POPE/POPG (3:1) bilayers. The findings of our investigation indicate that the AapA1-28 protein does not adopt a vertical orientation upon membrane insertion; rather, it assumes an angled conformation, with the side chain of Lys-23 directed toward the upper layer of the membrane. This non-transmembrane conformation of AapA1-28 protein impedes its ability to form pores within the membrane, resulting in reduced toxicity towards Escherichia coli. These results suggest that C-Terminal positively charged residues are essential for electrostatic binding to the negatively charged head group of bottom bilayer membrane, which stabilize the transmembrane conformation. These outcomes contribute to our comprehension of the impact of C-terminal charged residues on the structure and functionality of membrane-associated proteins, and provide an improved understanding of how protein sequence influences the antimicrobial effect.

Uptake, distribution, and elimination of selenite in earthworm Eisenia fetida at sublethal concentrations based on toxicokinetic model.

Natural and anthropogenic causes have promoted the rapid increase in environmental selenium (Se) levels, and the complex Se metabolism and dynamic in organisms make it challenging to evaluate the toxicity and ecological risks. In this study, the kinetics of selenite in earthworm Eisenia fetida were investigated based on toxicokinetic (TK) model (uptake-elimination phases: 14-14 days). The results showed the highest sub-tissue Se concentrations in pre-clitellum (PC), post-clitellum (PoC) parts, and total earthworms were 95.71, 70.40, and 79.94 mg/kg, respectively, which indicates the distinctive Se uptake capacities of E. fetida. Se kinetic rates in PCs were faster than that of the total E. fetida for both uptake (Kus = 0.30-0.80 mg/kg/day) and elimination phases (Kee = 0.024-0.056 mg/kg/day). Longer half-life times (LT1/2) were observed in the total earthworms (17.85-47.15 d) than PCs (12.28-29.22 d), while non-significant difference was found for the kinetic Se bioaccumulation factor (BAFk) in PC and total earthworms (12-19), which demonstrates that Se can be efficiently bioaccumulated and eliminated in earthworm PC part. Besides, the significant increase Se concentration in PoC with rapid elimination in PC also illustrates that earthworms can alleviate the Se stress by the transformation strategy of Se from the head to tail tissues. In conclusion, the investigation of Se kinetic accumulation and elimination characteristics in this study is helpful for understanding the metabolism and detoxification processes of Se in earthworms, and also providing a theoretical basis for further Se risk assessment using TK model.

EVlncRNA-Dpred: improved prediction of experimentally validated lncRNAs by deep learning.

Long non-coding RNAs (lncRNAs) played essential roles in nearly every biological process and disease. Many algorithms were developed to distinguish lncRNAs from mRNAs in transcriptomic data and facilitated discoveries of more than 600 000 of lncRNAs. However, only a tiny fraction (<1%) of lncRNA transcripts (~4000) were further validated by low-throughput experiments (EVlncRNAs). Given the cost and labor-intensive nature of experimental validations, it is necessary to develop computational tools to prioritize those potentially functional lncRNAs because many lncRNAs from high-throughput sequencing (HTlncRNAs) could be resulted from transcriptional noises. Here, we employed deep learning algorithms to separate EVlncRNAs from HTlncRNAs and mRNAs. For overcoming the challenge of small datasets, we employed a three-layer deep-learning neural network (DNN) with a K-mer feature as the input and a small convolutional neural network (CNN) with one-hot encoding as the input. Three separate models were trained for human (h), mouse (m) and plant (p), respectively. The final concatenated models (EVlncRNA-Dpred (h), EVlncRNA-Dpred (m) and EVlncRNA-Dpred (p)) provided substantial improvement over a previous model based on support-vector-machines (EVlncRNA-pred). For example, EVlncRNA-Dpred (h) achieved 0.896 for the area under receiver-operating characteristic curve, compared with 0.582 given by sequence-based EVlncRNA-pred model. The models developed here should be useful for screening lncRNA transcripts for experimental validations. EVlncRNA-Dpred is available as a web server at https://www.sdklab-biophysics-dzu.net/EVlncRNA-Dpred/index.html, and the data and source code can be freely available along with the web server.

Mechanical stretching boosts expansion and regeneration of intestinal organoids through fueling stem cell self-renewal.

Intestinal organoids, derived from intestinal stem cell self-organization, recapitulate the tissue structures and behaviors of the intestinal epithelium, which hold great potential for the study of developmental biology, disease modeling, and regenerative medicine. The intestinal epithelium is exposed to dynamic mechanical forces which exert profound effects on gut development. However, the conventional intestinal organoid culture system neglects the key role of mechanical microenvironments but relies solely on biological factors. Here, we show that adding cyclic stretch to intestinal organoid cultures remarkably up-regulates the signature gene expression and proliferation of intestinal stem cells. Furthermore, mechanical stretching stimulates the expansion of SOX9+ progenitors by activating the Wnt/ß-Catenin signaling. These data demonstrate that the incorporation of mechanical stretch boosts the stemness of intestinal stem cells, thus benefiting organoid growth. Our findings have provided a way to optimize an organoid generation system through understanding cross-talk between biological and mechanical factors, paving the way for the application of mechanical forces in organoid-based models.

Gold nanoclusters-loaded hydrogel formed by dimeric hydrogen bonds crosslinking: A novel strategy for multidrug-resistant bacteria-infected wound healing.

Restoring skin integrity after wound infection remains a tougher health challenge due to the uncontrolled antibiotic-resistant pathogens caused by antibiotic abuse. Herein, an injectable hydrogel with dual antibacterial and anti-inflammatory activities composed of gold nanoclusters (GNCs) and carbomer (CBM) is developed for wound dressing to overcome multidrug-resistant infection. Firstly, both experimental investigations and molecular dynamics simulation validate the protonation state of 6-mercaptohexanoic acid (MHA) ligands play an important role in its antibacterial action of GNCs. The self-organizing GNCs-CBM composite hydrogel is then spontaneously cross-linked by the dimeric hydrogen bonds (H-bonds) between the MHA ligands and the acrylic acid groups of CBM. Benefitting from the dimeric H-bonds, the hydrogel becomes thickening enough as an ideal wound dressing and the GNCs exist in the hydrogel with a high protonation level that contributes to the enhanced bactericidal function. In all, by combining bactericidal and immunomodulatory actions, the GNCs-CBM hydrogel demonstrated excellent synergy in accelerating wound healing in animal infection models. Hence, the dimeric H-bonds strengthening strategy makes the GNCs-CBM hydrogel hold great potential as a safe and effective dressing for treating infected wounds.

Molecular dynamics simulations to study the role of biphenylalanine in promoting the antibacterial activity of ultrashort peptides.

The hydrophobic amino acid biphenylalanine (B) plays a key role in the antibacterial activity of ultrashort peptides. In this study, the interactions of tetrapeptide BRBR-NH2 (BRBR) and pentapeptide BRBRB-NH2 (BRBRB) with dioleoylphosphatidylcholine/dioleoylphosphatidylglycerol (DOPC/DOPG) mixed model membrane were studied by molecular dynamics simulation to assess the role of biphenylalanine in promoting the antibacterial activity of ultrashort peptides. At low peptide concentrations, both peptides presented amphiphilic conformations; residues B of the pentapeptide approached the membrane faster than those of the tetrapeptide and made more contacts with the membrane; BRBRB exhibited stronger membrane affinity than BRBR. However, due to the low peptide concentrations, the effects of these two peptides on the membrane were not significantly different. At high peptide concentrations, the strong affinity of BRBRB made it have more interaction with membrane than BRBR and most residues B of BRBRB inserted into the membrane; BRBRB was more prone to aggregation and caused the membrane more disordered and thinner than BRBR. Hydrophobic residues often act as anchors in the antibacterial activity of ultrashort antimicrobial peptides. Adding a hydrophobic residue B to the C-terminal of BRBR could improve the ability of the peptide to "grasp" the membrane. At high peptide concentrations, the addition of residue B might enhance the antibacterial activity of the peptide. Thus, our results will be helpful in designing efficient antibacterial drugs.

Two-dimensional ZnO/BlueP van der Waals heterostructure used for visible-light driven water splitting: A first-principles study.

Solar driven water splitting for hydrogen generation has been considered as an important method for collecting clean energy. Herein, based on first-principles calculations, we propose that ZnO/BlueP van der Waals heterostructure can realize overall water splitting reaction for hydrogen generation. Strikingly, the band-gap of 1.83 eV is appropriate, and band alignments straddle the water redox potentials, ensuring the occurrence of hydrogenevolutionreaction and oxygen evolution reaction. Charge density distribution and carrier mobility exhibit significant charge separation and transfer. Visible-light response is improved compared with those of the isolated monolayers. Moreover, hydrogenevolutionreaction is actually realized on the ZnO layer, while oxygen evolution reaction is implemented on the BlueP layer. Through the investigation of the adsorption and dissociation reactions of H2O, we observe that two neighboring H*s prefer to combine to form H2 by overcoming a lowered energy barrier of 0.75 eV. Strain effect indicates that the lateral compressive strain of -4% to 0% and the vertical tensile strain of 0% to +6% can effectively tune band-gap and band alignments. The results indicate that ZnO/BlueP vdW heterostructure is probable highly efficient photoelectric material used for visible-light driven water splitting for hydrogen generation.

From "Dark Matter" to "Star": Insight Into the Regulation Mechanisms of Plant Functional Long Non-Coding RNAs.

Long non-coding RNAs (lncRNAs) play a vital role in a variety of biological functions in plant growth and development. In this study, we provided an overview of the molecular mechanisms of lncRNAs in interacting with other biomolecules with an emphasis on those lncRNAs validated only by low-throughput experiments. LncRNAs function through playing multiple roles, including sponger for sequestering RNA or DNA, guider or decoy for recruiting or hijacking transcription factors or peptides, and scaffold for binding with chromatin modification complexes, as well as precursor of microRNAs or small interfering RNAs. These regulatory roles have been validated in several plant species with a comprehensive list of 73 lncRNA-molecule interaction pairs in 16 plant species found so far, suggesting their commonality in the plant kingdom. Such initial findings of a small number of functional plant lncRNAs represent the beginning of what is to come as lncRNAs with unknown functions were found in orders of magnitude more than proteins.

Ligand-induced structural changes analysis of ribose-binding protein as studied by molecular dynamics simulations.

BACKGROUND: The ribose-binding protein (RBP) from Escherichia coli is one of the representative structures of periplasmic binding proteins. Binding of ribose at the cleft between two domains causes a conformational change corresponding to a closure of two domains around the ligand. The RBP has been crystallized in the open and closed conformations. OBJECTIVE: With the complex trajectory as a control, our goal was to study the conformation changes induced by the detachment of the ligand, and the results have been revealed from two computational tools, MD simulations and elastic network models. METHODS: Molecular dynamics (MD) simulations were performed to study the conformation changes of RBP starting from the open-apo, closed-holo and closed-apo conformations. RESULTS: The evolution of the domain opening angle θ clearly indicates large structural changes. The simulations indicate that the closed states in the absence of ribose are inclined to transition to the open states and that ribose-free RBP exists in a wide range of conformations. The first three dominant principal motions derived from the closed-apo trajectories, consisting of rotating, bending and twisting motions, account for the major rearrangement of the domains from the closed to the open conformation. CONCLUSIONS: The motions showed a strong one-to-one correspondence with the slowest modes from our previous study of RBP with the anisotropic network model (ANM). The results obtained for RBP contribute to the generalization of robustness for protein domain motion studies using either the ANM or PCA for trajectories obtained from MD.

EVLncRNAs 2.0: an updated database of manually curated functional long non-coding RNAs validated by low-throughput experiments.

Long non-coding RNAs (lncRNAs) play important functional roles in many diverse biological processes. However, not all expressed lncRNAs are functional. Thus, it is necessary to manually collect all experimentally validated functional lncRNAs (EVlncRNA) with their sequences, structures, and functions annotated in a central database. The first release of such a database (EVLncRNAs) was made using the literature prior to 1 May 2016. Since then (till 15 May 2020), 19 245 articles related to lncRNAs have been published. In EVLncRNAs 2.0, these articles were manually examined for a major expansion of the data collected. Specifically, the number of annotated EVlncRNAs, associated diseases, lncRNA-disease associations, and interaction records were increased by 260%, 320%, 484% and 537%, respectively. Moreover, the database has added several new categories: 8 lncRNA structures, 33 exosomal lncRNAs, 188 circular RNAs, and 1079 drug-resistant, chemoresistant, and stress-resistant lncRNAs. All records have checked against known retraction and fake articles. This release also comes with a highly interactive visual interaction network that facilitates users to track the underlying relations among lncRNAs, miRNAs, proteins, genes and other functional elements. Furthermore, it provides links to four new bioinformatics tools with improved data browsing and searching functionality. EVLncRNAs 2.0 is freely available at https://www.sdklab-biophysics-dzu.net/EVLncRNAs2/.

Influence of Different Aromatic Hydrophobic Residues on the Antimicrobial Activity and Membrane Selectivity of BRBR-NH2 Tetrapeptide.

The ultrashort linear antimicrobial tetrapeptide BRBR-NH2 with an unnatural residue biphenylalanine (B) has potent and rapid antimethicillin-resistant Staphylococcus aureus (MRSA) activity but lacks hemolytic activity. The anti-MRSA activity of BRBR-NH2 is 8-fold more potent than that of WRWR-NH2 and 16-fold more potent than that of FRFR-NH2. However, how to influence their antimicrobial activities and mechanisms through the substitution of different aromatic hydrophobic residues is still unclear. In this work, to study the effects of varying hydrophobic interactions and membrane selectivities of BRBR-NH2, we performed multiple long-time (1000 ns) molecular dynamics (MD) simulations to investigate the interactions of a red blood cell (RBC) membrane and a Gram-positive bacterial cell membrane with three different tetrapeptides (BRBR-NH2, WRWR-NH2, and FRFR-NH2) under different ratios of peptides and lipids and also explored the changes in the membrane and structural characteristics of peptides. The binding energy results show that BRBR-NH2 interacts weakly with the RBC membrane, while not all BRBR-NH2 can be adsorbed to the RBC membrane surface. The MD simulation results produced significant local membrane thinning of multiBRBR-NH2 peptides in the Gram-positive bacterial cell membrane. An in-depth analysis of structural features and peptide-membrane interactions suggests that the aggregation of BRBR-NH2 on the membrane surface plays a crucial role in the destruction of the cell membrane. Taken together with the observed local membrane thinning, the in-depth analysis demonstrated that the interactions between the lipid bilayer and the BRBR-NH2 aggregation surface result in a local disturbance of the membrane structure. It can be concluded that the high anti-MRSA activity of BRBR-NH2 is attributed to the aggregation of BRBR-NH2 on the membrane surface. On the other hand, WRWR-NH2 and FRFR-NH2 peptides tend to bind with the membrane surface in a monomeric form and cover the membrane surface in a carpet-like manner. Therefore, these results provide an advanced microscopic understanding of how hydrophobic interactions or hydrophobic residues affect the antimicrobial activity and mechanism of antimicrobial peptides (AMPs).

A Gold Nanocluster Constructed Mixed-Metal Metal-Organic Network Film for Combating Implant-Associated Infections.

The development of modular strategies for programming self-assembled supramolecular architectures with distinct structural and functional features is of immense scientific interest. We reported on the intrinsic antibacterial capability of anionic amphiphilic gold nanoclusters (GNCs) capped by para-mercaptobenzoic acid, which was closely related to the protonation level of terminal carboxylate groups. By using of the metal-ligand coordination-driven and solvent evaporation-induced self-assembly, we constructed GNCs-based mixed-metal metal-organic network (MM-MON) films on titanium disks as antibacterial nanocoatings. Taking the reasonable utilization of tetravalent metal ions M4+ (Ti, Zr, Hf; hard Lewis acid) and bactericidal divalent metal ions M2+ (Cu, Zn; borderline acid) co-incorporated metal-carboxylate coordination bonds, the MM-MON films exhibited superior stability due to the robust M4+-O bonds and M2+ releasing behavior resulting from the labile M2+-O coordinating. Together, the MM-MON films integrated the bacteria-responsive character of GNCs, exceptional chemical stability, and greatly enhanced antibacterial activity, ultimately killing adherent bacteria and initiating a self-defensive function. In a rat model for subcutaneous implant-associated infection, the MM-MON nanocoating showed an approximately 2 and 1 log lower multidrug-resistant Staphylococcus aureus implant and tissue colonization, respectively. The generalizable modular strategy of the GNC-metal networks is amenable to facilitate the functionalization of metal surfaces for combating implant-associated infections.

Genetic variability of human angiotensin-converting enzyme 2 (hACE2) among various ethnic populations.

BACKGROUND: There appears to be large regional variation for susceptibility, severity, and mortality for COVID-19 infections. Numerous potential factors could explain the wide variability in the number of infections and death among the countries. We examined genetic differences in the human angiotensin-converting enzyme 2 (hACE2) gene, as its receptor serves as a cellular entry for SARS-CoV-2. At present, there is a paucity of data regarding the differences for ACE2 polymorphisms and expression levels between ethnicities. METHODS: We compared the allele frequency of mutations between European and East Asians. Molecular dynamic simulation were performed to investigate the influences of significant mutant on protein structure. The binding free energies were calculated between S protein and hACE2. We also examined hACE2 gene expression in eight global populations from HapMap3. RESULTS: Four missense mutations showed significant minor allele frequency difference between Asians and Caucasians. Molecular dynamic demonstrated that two of these variants (K26R and I468V) may affect binding characteristics between S protein of the virus and hACE2 receptor. We also noted marginal differences in gene expression for some populations in HapMap3 as compared to the Chinese population. CONCLUSION: Our studies reveal subtle changes in the genetics of hACE2 between human populations, but the magnitude of the difference was small and the significance is not clear in the absence of further in vitro and functional studies.

Interplay of hydrophobic and hydrophilic interactions in sequence-dependent cell penetration of spontaneous membrane-translocating peptides revealed by bias-exchange metadynamics simulations.

Spontaneous Membrane Translocating Peptides (SMTPs) can translocate silently across the bilayer and, thus, have the best potential to improve the delivery of therapeutic molecules to cells without toxicity. However, how their translocation mechanisms are affected by a specific peptide sequence remains poorly understood. Here, bias-exchange metadynamics simulations were employed to investigate the translocation mechanisms of five SMTPs with the same composition of amino acids (LLRLR, LRLLR, LLLRR, RLLLR, and LRLRL). Simulation results yield sequence-dependent free energy barrier using the FESs along the z-directional distance. An in-depth analysis of sequence-dependent interactions in different regions of the bilayers indicates that the free-energy barrier height of a specific sequence is resulted from the accessibility balance of isolated or clustered hydrophobic residues (L) and hydrophilic residues (R) that leads to different levels of resistance for moving of a peptide into the hydrophobic center of the membrane. At the maximal of the free-energy barrier, all peptides have a conformation parallel to the membrane surface with the barrier height determined by their affinity to the hydrophobic region. The appropriate bilayer perturbation and GDM+ pairing are beneficial for peptide translocation. These results provide an improved microscopic understanding of how peptide sequence influences the translocation efficiency and mechanism.

Experimentally Validated Plant lncRNAs in EVLncRNAs Database.

Plant long noncoding RNAs (lncRNAs) play important functional roles in various biological processes. Most databases deposit all plant lncRNA candidates produced by high-throughput experimental and/or computational techniques. There are several databases for experimentally validated lncRNAs. However, these databases are small in scale (with a few hundreds of lncRNAs only) and specific in their focuses (plants, diseases, or interactions). Thus, we established EVLncRNAs by curating lncRNAs validated by low-throughput experiments (up to May 1, 2016) and integrating specific databases (lncRNAdb, LncRANDisease, Lnc2Cancer, and PLNIncRBase) with additional functional and disease-specific information not covered previously. The current version of EVLncRNAs contains 1543 lncRNAs from 77 species, including 428 plant lncRNAs from 44 plant species. Compared to PLNIncRBase, our dataset does not contain any lncRNAs from microarray and deep sequencing. Moreover, 40% of entries contain new information (interaction and additional information from NCBI and Ensembl). The database allows users to browse, search, and download as well as to submit experimentally validated lncRNAs. The database is available at http://biophy.dzu.edu.cn/EVLncRNAs .