microRNA 1307 Is a Potential Target for SARS-CoV-2 Infection: An Model.

microRNAs (miRs) are proposed as critical molecular targets in SARS-CoV-2 infection. Our recent studies identified seven SARS-CoV-2 specific miR-like sequences, which are highly conserved with humans, including miR-1307-3p, with critical roles in COVID-19. In this current study, Vero cells were infected with SARS-CoV-2, and miR expression profiles were thereafter confirmed by qRT-PCR.

The Role of CDK4 in the Pathogenesis of Pancreatic Cancer.

Pancreatic cancer (PC) continues to have the lowest overall survival and the lack of effective early diagnosis. Cyclin-dependent kinase 4 (CDK4) plays a fundamental role in the orderly progression of the cell cycle, binding to cyclin D to promote the progression through the G1/2 transition. The inhibition of CDK4/6 has therefore gained substantial interest in the hope of new and effective therapeutics in multiple cancers, such as advanced metastatic breast cancer.

MicroRNAs for Virus Pathogenicity and Host Responses, Identified in SARS-CoV-2 Genomes, May Play Roles in Viral-Host Co-Evolution in Putative Zoonotic Host Species.

Our recent study identified seven key microRNAs (miR-8066, 5197, 3611, 3934-3p, 1307-3p, 3691-3p, 1468-5p) similar between SARS-CoV-2 and the human genome, pointing at miR-related mechanisms in viral entry and the regulatory effects on host immunity. To identify the putative roles of these miRs in zoonosis, we assessed their conservation, compared with humans, in some key wild and domestic animal carriers of zoonotic viruses, including bat, pangolin, pig, cow, rat, and chicken. Out of the seven miRs under study, miR-3611 was the most strongly conserved across all species; miR-5197 was the most conserved in pangolin, pig, cow, bat, and rat; miR-1307 was most strongly conserved in pangolin, pig, cow, bat, and human; miR-3691-3p in pangolin, cow, and human; miR-3934-3p in pig and cow, followed by pangolin and bat; miR-1468 was most conserved in pangolin, pig, and bat; while miR-8066 was most conserved in pangolin and pig.

Inhibition on JNK Mimics Silencing of Wnt-11 Mediated Cellular Response in Androgen-Independent Prostate Cancer Cells.

Prostate cancer (PCa) is one of the most common cancers among men, and one of the leading causes of cancer death for men. The c-Jun N-terminal kinase (JNK) pathway is required for several cellular functions, such as survival, proliferation, differentiation, and migration. Wnt-11, a member of the Wnt family, has been identified for its upregulation in PCa; however, downstream signalling of Wnt-11 remains to be fully characterized.

The Prediction of miRNAs in SARS-CoV-2 Genomes: hsa-miR Databases Identify 7 Key miRs Linked to Host Responses and Virus Pathogenicity-Related KEGG Pathways Significant for Comorbidities.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a member of the family, which causes COVID-19 disease. SARS-CoV-2 pathogenicity in humans leads to increased mortality rates due to alterations of significant pathways, including some resulting in exacerbated inflammatory responses linked to the "cytokine storm" and extensive lung pathology, as well as being linked to a number of comorbidities. Our current study compared five SARS-CoV-2 sequences from different geographical regions to those from SARS, MERS and two cold viruses, OC43 and 229E, to identify the presence of miR-like sequences.

Modelling, inference and big data in biophysics.

In recognition of the increasing importance of big data in biophysics, a new session called 'Modelling, inference, big data' is incorporated into the IUPAB/EBSA Congress on 18 July 2017 at Edinburgh, UK.

The interaction of Wnt-11 and signalling cascades in prostate cancer.

Prostate cancer (PCa) is the second most common cancer among the male population. Conventional therapies target androgen signalling, which drives tumour growth; however, they provide limited survival benefits for patients. It is essential, therefore, to develop a more specific biomarker than the current gold standard, PSA testing.

Binding modes of diketo-acid inhibitors of HIV-1 integrase: a comparative molecular dynamics simulation study.

HIV-1 integrase (IN) has become an attractive target since drug resistance against HIV-1 reverse transcriptase (RT) and protease (PR) has appeared. Diketo acid (DKA) inhibitors are potent and selective inhibitors of HIV-1 IN: however the action mechanism is not well understood. Here, to study the inhibition mechanism of DKAs we performed 10 ns comparative molecular dynamics simulations on HIV-1 IN bound with three most representative DKA inhibitors: Shionogi inhibitor, S-1360 and two Merck inhibitors L-731,988 and L-708,906.

The distinct conformational dynamics of K-Ras and H-Ras A59G.

Ras proteins regulate signaling cascades crucial for cell proliferation and differentiation by switching between GTP- and GDP-bound conformations. Distinct Ras isoforms have unique physiological functions with individual isoforms associated with different cancers and developmental diseases. Given the small structural differences among isoforms and mutants, it is currently unclear how these functional differences and aberrant properties arise.

Computational analysis of phosphopeptide binding to the polo-box domain of the mitotic kinase PLK1 using molecular dynamics simulation.

The Polo-Like Kinase 1 (PLK1) acts as a central regulator of mitosis and is over-expressed in a wide range of human tumours where high levels of expression correlate with a poor prognosis. PLK1 comprises two structural elements, a kinase domain and a polo-box domain (PBD). The PBD binds phosphorylated substrates to control substrate phosphorylation by the kinase domain.

Unraveling evolutionary constraints: a heterogeneous conservation in dynamics of the titin Ig domains.

The giant protein titin, which comprises immunoglobulin (Ig) domains, acts as a bidirectional spring in muscle. The unfolding of Ig domains has been extensively studied, but their dynamics under native states have not been well-characterized. We performed molecular dynamics simulation on a single titin Ig domain and multi-domains.

A network of dynamically conserved residues deciphers the motions of maltose transporter.

The maltose transporter of Escherichia coli is a member of the ATP-binding cassette (ABC) transporter superfamily. The crystal structures of maltose transporter MalK have been determined for distinct conformations in the presence and absence of the ligand ATP, and other interacting proteins. Using the distinct MalK structures, normal mode analysis was performed to understand the dynamics behavior of the system.

Dynamics of conserved waters in human Hsp90: implications for drug design.

The flexibility of a promising protein target, human heat shock protein 90 (Hsp90), is investigated by molecular dynamics simulations. These simulations focus on: (i) the interactions between the protein and conserved water molecules; and (ii) the interactions of the ligand PU3, the conserved water molecules and the protein. This is followed by a virtual screening docking study of the PU3 family of compounds and Hsp90 incorporating several conserved water molecules.

Classification of proteins based on similarity of two-dimensional protein maps.

Data reduction techniques are now a vital part of numerical analysis and principal component analysis is often used to identify important molecular features from a set of descriptors. We now take a different approach and apply data reduction techniques directly to protein structure. With this we can reduce the three-dimensional structural data into two-dimensions while preserving the correct relationships.

The effect of solvation on biomolecular conformation: 2-amino-1-phenylethanol.

Small molecule neurotransmitters form one the most important classes of pharmaceutical molecules. While the behavior of these molecules in their neutral forms in the gas phase is well understood, their behavior in more biologically relevant scenarios (protonated and in aqueous solution) has received comparatively little attention. Here we address this problem by using molecular mechanics simulations to build up a detailed picture of the conformational behavior of 2-amino-1-phenylethanol, a noradrenaline analogue, in aqueous solution in both its neutral and protonated forms.

Modeling Aromatic Liquids: Toluene, Phenol, and Pyridine.

Aromatic groups are now acknowledged to play an important role in many systems of interest. However, existing molecular mechanics methods provide a poor representation of these groups. In a previous paper, we have shown that the molecular mechanics treatment of benzene can be improved by the incorporation of an explicit representation of the aromatic π electrons.

Role of aromatic amino acids in protein-nucleic acid recognition.

Statistical analysis of structures from the PBD has been used to examine the role that the aromatic amino acids play in protein-nucleic acid recognition. In protein-DNA complexes, the residues Phe and His are found to bind selectively to the DNA chain--Phe to A and T, and His to T and G. The preferred binding modes are identified, and the interactions involving Phe are shown to be important in the transcription process.

Characterization and tissue-specific expression of two lepidopteran farnesyl diphosphate synthase homologs: implications for the biosynthesis of ethyl-substituted juvenile hormones.

The sesquiterpenoid juvenile hormone (JH) regulates insect development and reproduction. Most insects produce only one chemical form of JH, but the Lepidoptera produce four derivatives featuring ethyl branches. The biogenesis of these JHs requires the synthesis of ethyl-substituted farnesyl diphosphate (FPP) by FPP synthase (FPPS).

Diketoacid HIV-1 integrase inhibitors: An ab initio study.

The stable tautomeric forms of two representative arene-substituted diketoacid HIV-1 integrase inhibitors, 5-ClTEP and L-731,988, were investigated by B3LYP with 6-31G*, 6-31G(d,p), and 6-31+G(d,p) basis sets. Optimization with MP2/6-31G* was also performed for 5-ClTEP. The solvation effect was considered using a conductor-like screening model.

The Structure of Liquid Benzene.

The interactions of aromatic groups have been identified as playing a crucial role in many systems of interest. Unfortunately, conventional atom-centered force fields provide only an approximate representation of these molecules owing to their failure to consider the quadrupole moment arising from the π electrons. In this paper the structure of liquid benzene, the prototypical aromatic system, is investigated using a novel approach to Monte Carlo simulation, parametrized against experimental thermodynamic data, which incorporates an explicit representation of the aromatic π electrons.

A solvent induced mechanism for conformational change.

Molecular dynamics simulations have been used to investigate the dynamic behaviour of two small molecule neurotransmitter analogues in aqueous solution, leading to the elucidation of a mechanism for conformational change which is driven by the presence of the solvent molecules.

Kanamycin reveals the role played by glutamate receptors in shaping plant resource allocation.

Ionotropic glutamate receptors (iGluRs) play important roles in neurotransmission in animals. There is growing evidence that iGluRs also play important roles in plants. Using a chemical genetics approach, which combined a pH-homeostasis mutant of Arabidopsis thaliana (de-etiolated3), several different iGluR agonists, molecular modelling, and reporter gene expression in transgenic plants, we provide evidence that iGluR agonism can induce dramatic changes in plant development and metabolism.

Structure, electronic circular dichroism and Raman optical activity in the gas phase and in solution: a computational and experimental investigation.

A computational (ab initio and molecular dynamics) and experimental exploration of the relative importance of molecular conformation and explicit solvent effects on the electronic circular dichroism (ECD) of chiral molecules, is presented. The exploration includes an assessment of the validity of angular correlation (sector) rules linking ECD to molecular conformation. It is based upon studies of 1-(R) phenylethanol (including its Raman optical activity spectrum), the corresponding 'benchmark' base, 1-(R)-phenylethylamine and its protonated cation; their hydrated clusters in the gas phase; and their non-polar and aqueous solutions.

Helix-forming carbohydrate amino acids.

[reaction: see text] The solution-phase conformational properties of tetrameric and octameric chains of C-glycosyl alpha-d-lyxofuranose configured tetrahydrofuran amino acids (where the C-2 and C-5 substituents on the tetrahydrofuran ring are trans to each other) were examined using NMR and IR and CD in organic solvents. Studies by NMR and IR demonstrated that in chloroform solution, the tetramer 7 does not adopt a hydrogen-bonded conformation whereas the octamer 10 populates a well-defined helical secondary structure stabilized by 16-membered (i, i - 3) interresidue hydrogen bonds, similar to a pi-helix. Circular dichroism studies in trifluoroethanol are consistent with this conformation for the octamer 10, and also indicate that the tetramer 7 adopts a rigid conformation not stabilized by hydrogen bonds.

The function of the amino terminal domain in NMDA receptor modulation.

N-methyl-D-aspartate (NMDA) receptors are ligand-gated channels important in neurotransmission which are activated by the combined presence of glutamate and glycine. They are comprised of four subunits that form a dimer of dimers. The activity of NMDA receptors is modulated by a variety of endogenous ligands such as zinc ions, phenylethanolamines, polyamines and protons.