自引率: 6.3%
被引量: 2206
通过率: 暂无数据
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国人发稿量: 10
投稿须知/期刊简介:
Journal of Molecular Recognition (JMR) publishes original research papers and reviews describing molecular recognition phenomena in biology. Molecular recognition refers to the non-covalent specific interaction between two or more biological molecules exemplified by receptor-ligand antigen-antibody DNA-protein sugar-lectin and many other interactions. Biomolecular interactions are studied both at the structural level in terms of atomic coordinates and at the functional level in terms of kinetic and equilibrium binding constants. The journal will focus on studies that aim to achieve a complete description of recognition sites in terms of the structure dynamics and activity of biomolecules. JMR will provide a forum for research papers in the field of quantitative biomolecular interaction analysis using biosensors and other solution or surface-mediated experimental techniques including microcalorimetry. Since the understanding of molecular recognition at a microscopic level can be aided by theoretical approaches including electrostatic analysis and molecular dynamics and free energy simulations these aspects will also be covered. In addition submission of manuscripts related to the application of other instrumental methods such as HPLC LC-MS CE-MS employed in the elucidation of the biophysical basis of the pathways of molecular recognition between interacting biological molecules are encouraged. The design synthesis and application of structural or topological mimics of naturally occurring molecules in the characterisation of molecular recognition processes represents a further aspect encompassed by the Journal. These technologies in conjunction with crystallography NMR and site directed mutagenesis are providing new insights into the correlation between atomic structure and binding energy and pave the way to improved computer simulation docking and molecular design of biologically active molecules. JMR will also publish articles on the applications of chemically and biologically generated molecular libraries to the study of biomolecular interactions and the creation of novel functions.
期刊描述简介:
Journal of Molecular Recognition (JMR) publishes original research papers and reviews describing substantial advances in our understanding of molecular recognition phenomena in life sciences, covering all aspects from biochemistry, molecular biology, medicine, and biophysics. The research may employ experimental, theoretical and/or computational approaches. The focus of the journal is on recognition phenomena involving biomolecules and their biological / biochemical partners rather than on the recognition of metal ions or inorganic compounds. Molecular recognition involves non-covalent specific interactions between two or more biological molecules, molecular aggregates, cellular modules or organelles, as exemplified by receptor-ligand, antigen-antibody, nucleic acid-protein, sugar-lectin, to mention just a few of the possible interactions. The journal invites manuscripts that aim to achieve a complete description of molecular recognition mechanisms between well-characterized biomolecules in terms of structure, dynamics and biological activity. Such studies may help the future development of new drugs and vaccines, although the experimental testing of new drugs and vaccines falls outside the scope of the journal. Manuscripts that describe the application of standard approaches and techniques to design or model new molecular entities or to describe interactions between biomolecules, but do not provide new insights into molecular recognition processes will not be considered. Similarly, manuscripts involving biomolecules uncharacterized at the sequence level (e.g. calf thymus DNA) will not be considered. Typical techniques would include synthesis of topological mimics, site directed mutagenesis or molecular imprinting, together with biophysical methods for the quantitative measurement of molecular interactions. Specific methods such as AFM, Optical Tweezers, SPR, Biosensors and Microcalorimetry, and the range of analytical methods such as NMR, MRI, MS, GC, LC, HPLC, PET, and Crystallography may be used to establish the mechanisms, dynamics and forces of molecular recognition processes. Theoretical and Computational Methods aid the modeling, prediction, simulation and design of molecular recognition processes. Mechanistic understanding at a molecular level can be aided by computational approaches such as molecular electrostatic analysis, molecular dynamics simulations and free energy calculations.
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TAZ-hTrap: A Rationally Designed, Disulfide-Stapled Tead Helical Hairpin Trap to Selectively Capture Hippo Signaling Taz With Potent Antigynecological Tumor Activity.
Transcriptional enhanced associate domain (Tead)-mediated Hippo signaling pathway regulates diverse physiological processes; its dysfunction has been implicated in an increasing number of human gynecological cancers. The transcriptional coactivator with PDZ-binding motif (Taz) binds to and then activates Tead through forming a three-helix bundle (THB) at their complex interface. The THB is defined by a double-helical hairpin from Tead and a single α-helix from Taz, serving as the key interaction hotspot between Tead and Taz. In the present study, the helical hairpin was derived from Tead protein to generate a hairpin segment, which is a 25-mer polypeptide consisting of a longer helical arm-1 and a shorter helical arm-2 as well as a flexible loop linker between them. Dynamics simulation and energetics characterization revealed that the hairpin peptide is intrinsically disordered when splitting from its protein context, thus incurring a large entropy penalty upon binding to Taz α-helix. A disulfide bridge was introduced across the two helical arms of hairpin peptide to obtain a strong binder termed TAZ-hTrap, which can maintain in a considerably structured, native-like conformation in unbound state, and the entropy penalty was minimized by disulfide stapling to effectively improve its affinity toward the α-helix. These computational findings can be further substantiated by circular dichroism and fluorescence polarization at molecular level, and viability assay also observed a potent cytotoxic effect on diverse human gynecological tumors at cellular level. In addition, we further demonstrated that the TAZ-hTrap has a good selectivity for its cognate Taz over other noncognate proteins that share a high conservation with the Taz α-helix.
被引量：- 发表：1970
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Microsecond Molecular Dynamics Simulation to Gain Insight Into the Binding of MRTX1133 and Trametinib With KRAS(G12D) Mutant Protein for Drug Repurposing.
被引量：- 发表：1970
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Investigating the Inhibition of Diindolylmethane Derivatives on SARS-CoV-2 Main Protease.
The SARS-CoV-2 main protease (Mpro) is an essential enzyme that promotes viral transcription and replication. Mpro conserved nature in different variants and its nonoverlapping nature with human proteases make it an attractive target for therapeutic intervention against SARS-CoV-2. In this work, the interaction mechanism between Mpro and diindolylmethane derivatives was investigated by molecular docking, enzymatic inhibition assay, UV-vis, fluorescence spectroscopy, and circular dichroism spectroscopy. Results of IC50 values show that 1p (9.87 μM) was the strongest inhibitor for Mpro in this work, which significantly inhibited the activity of Mpro. The binding constant (4.07 × 105 Lmol-1), the quenching constant (5.41 × 105 Lmol-1), and thermodynamic parameters indicated that the quenching mode of 1p was static quenching, and the main driving forces between 1p and Mpro are hydrogen bond and van der Waals force. The influence of molecular structure on the binding is investigated. Chlorine atoms and methoxy groups are favorable for the diindolylmethane derivative inhibitors of Mpro. This work confirms the changes in the microenvironment of Mpro by 1p, and provides clues for the design of potential inhibitors.
被引量：- 发表：1970
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Binding characteristics of the doxepin E/Z-isomers to the histamine H(1) receptor revealed by receptor-bound ligand analysis and molecular dynamics study.
Doxepin is an antihistamine and tricyclic antidepressant that binds to the histamine H1 receptor (H1R) with high affinity. Doxepin is an 85:15 mixture of the E- and Z-isomers. The Z-isomer is well known to be more effective than the E-isomer, whereas based on the crystal structure of the H1R/doxepin complex, the hydroxyl group of Thr1123.37 is close enough to form a hydrogen bond with the oxygen atom of the E-isomer. The detailed binding characteristics and reasons for the differences remain unclear. In this study, we analyzed doxepin isomers bound to the receptor following extraction from a purified H1R protein complexed with doxepin. The ratio of the E- and Z-isomers bound to wild-type (WT) H1R was 55:45, indicating that the Z-isomer was bound to WT H1R with an approximately 5.2-fold higher affinity than the E-isomer. For the T1123.37V mutant, the E/Z ratio was 89:11, indicating that both isomers have similar affinities. Free energy calculations using molecular dynamics (MD) simulations also reproduced the experimental results of the relative binding free energy differences between the isomers for WT and T1123.37V. Furthermore, MD simulations revealed that the hydroxyl group of T1123.37 did not form hydrogen bonds with the E-isomer, but with the adjacent residues in the binding pocket. Analysis of the receptor-bound doxepin and MD simulations suggested that the hydroxyl group of T1123.37 contributes to the formation of a chemical environment in the binding pocket, which is slightly more favorable for the Z-isomer without hydrogen bonding with doxepin.
被引量：- 发表：1970
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Measurement of protein concentration in bacteria and small organelles under a light transmission microscope.
Protein concentration (PC) is an essential characteristic of cells and organelles; it determines the extent of macromolecular crowding effects and serves as a sensitive indicator of cellular health. A simple and direct way to quantify PC is provided by brightfield-based transport-of-intensity equation (TIE) imaging combined with volume measurements. However, since TIE is based on geometric optics, its applicability to micrometer-sized particles is not clear. Here, we show that TIE can be used on particles with sizes comparable to the wavelength. At the same time, we introduce a new ImageJ plugin that allows TIE image processing without resorting to advanced mathematical programs. To convert TIE data to PC, knowledge of particle volumes is essential. The volumes of bacteria or other isolated particles can be measured by displacement of an external absorbing dye ("transmission-through-dye" or TTD microscopy), and for spherical intracellular particles, volumes can be estimated from their diameters. We illustrate the use of TIE on Escherichia coli, mammalian nucleoli, and nucleolar fibrillar centers. The method is easy to use and achieves high spatial resolution.
被引量：- 发表：1970
