Predicting subtype selectivity of dopamine receptor ligands with three-dimensional biologically relevant spectrum

2016 ◽  
Vol 88 (6) ◽  
pp. 859-872 ◽  
Author(s):  
Zheng-Kun Kuang ◽  
Shi-Yu Feng ◽  
Ben Hu ◽  
Dong Wang ◽  
Song-Bing He ◽  
...  
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Song-Bing He ◽  
Ben Hu ◽  
Zheng-Kun Kuang ◽  
Dong Wang ◽  
De-Xin Kong

An amendment to this paper has been published and can be accessed via a link at the top of the paper.


2010 ◽  
Vol 50 (11) ◽  
pp. 1970-1985 ◽  
Author(s):  
Qi Wang ◽  
Robert H. Mach ◽  
Robert R. Luedtke ◽  
David E. Reichert

1989 ◽  
Vol 32 (9) ◽  
pp. 2050-2058 ◽  
Author(s):  
Paul S. Charifson ◽  
J. Phillip Bowen ◽  
Steven D. Wyrick ◽  
Andrew J. Hoffman ◽  
Michael Cory ◽  
...  

Marine Drugs ◽  
2018 ◽  
Vol 16 (10) ◽  
pp. 384 ◽  
Author(s):  
Giuseppe Floresta ◽  
Emanuele Amata ◽  
Carla Barbaraci ◽  
Davide Gentile ◽  
Rita Turnaturi ◽  
...  

Sigma receptors are a fascinating receptor protein class whose ligands are actually under clinical evaluation for the modulation of opioid analgesia and their use as positron emission tomography radiotracers. In particular, peculiar biological and therapeutic functions are associated with the sigma-2 (σ2) receptor. The σ2 receptor ligands determine tumor cell death through apoptotic and non-apoptotic pathways, and the overexpression of σ2 receptors in several tumor cell lines has been well documented, with significantly higher levels in proliferating tumor cells compared to quiescent ones. This acknowledged feature has found practical application in the development of cancer cell tracers and for ligand-targeting therapy. In this context, the development of new ligands that target the σ2 receptors is beneficial for those diseases in which this protein is involved. In this paper, we conducted a search of new potential σ2 receptor ligands among a database of 1517 “small” marine natural products constructed by the union of the Seaweed Metabolite and the Chemical Entities of Biological Interest (ChEBI) Databases. The structures were passed through two filters that were constituted by our developed two-dimensional (2D) and three-dimensional Quantitative Structure-Activity Relationship (3D-QSAR) statistical models, and successively docked upon a σ2 receptor homology model that we built according to the FASTA sequence of the σ2/TMEM97 (SGMR2_HUMAN) receptor.


1993 ◽  
Vol 106 (1) ◽  
pp. 261-274 ◽  
Author(s):  
M.W. Goldberg ◽  
T.D. Allen

The structure of the nuclear pore complex (NPC) has been previously studied by many different electron microscopic techniques. Recently, scanning electron microscopes have been developed that can visualise biologically relevant structural detail at the same level of resolution as transmission electron microscopes and have been used to study NPC structure. We have used such an instrument to visualise directly the structure of both cytoplasmic and nucleoplasmic surfaces of the NPC of manually isolated amphibian oocyte nuclear envelopes that have been spread, fixed, critical point dried and coated with a thin fine-grained film of chromium or tantalum. We present images that directly show features of the NPC that are visible at each surface, including coaxial rings, cytoplasmic particles, plug/spoke complexes and the nucleoplasmic basket or fishtrap. Some cytoplasmic particles are rod-shaped or possibly “T”-shaped, can be quite long structures extending into the cytoplasm and may be joined to the coaxial ring at a position between each subunit. Both coaxial rings, which are proud of the membranes, can be exposed by light proteolytic digestion, revealing eight equal subunits each of which may be bipartite. We have determined that the nucleoplasmic filaments that make up the baskets are attached to the outer periphery of the coaxial ring at a position between each of its subunits. These filaments extend into the nucleoplasm and insert at the distal end to the smaller basket ring. The space left between adjacent basket filaments would exclude particles bigger than about 25 nm, which is consistent with the exclusion limit previously found for NPC-transported molecules.


2000 ◽  
Vol 6 (S2) ◽  
pp. 264-265
Author(s):  
J-F. Ménétret ◽  
D. G. Morgan ◽  
M. Radermacher ◽  
A. Neuhof ◽  
T. A. Rapoport ◽  
...  

Co-translational translocation at the endoplasmic reticulum (ER) plays a critical role in the targeting of both soluble and membrane proteins to their correct intra- and intercellular compartments. We are studying the 3D architecture of the ribosome-Sec61p complex (translocon), with the aim of understanding the physical mechanisms of gating and transport. To this end, we are using single particle electron cryo-microscopy and 3D reconstruction of frozen hydrated channel complexes, to obtain interpretable and biologically relevant maps.Previously, we have shown that both co- and post-translational translocation utilize a common central channel comprised of a ring-like Sec61p oligomer. Moreover, this channel morphology is shared with the related Sec YE complex from B. subtilus. Mass analysis, volume calculations and ribosome binding experiments suggest a stoichiometry of 3-4 Sec61p heterotrimers per ring. We currently favor 4 copies of the Sec61p complex per channel, as projection maps demonstrate 4 nearly equi-spaced peaks around the central pore.


Molecules ◽  
2019 ◽  
Vol 24 (21) ◽  
pp. 4003 ◽  
Author(s):  
Dong Wang ◽  
Ren-Yuan Hong ◽  
Mengyao Guo ◽  
Yi Liu ◽  
Nianhang Chen ◽  
...  

There is a continued need to develop new selective human monoamine oxidase (hMAO) inhibitors that could be beneficial for the treatment of neurological diseases. However, hMAOs are closely related with high sequence identity and structural similarity, which hinders the development of selective MAO inhibitors. “Three-Dimensional Biologically Relevant Spectrum (BRS-3D)” method developed by our group has demonstrated its effectiveness in subtype selectivity studies of receptor and enzyme ligands. Here, we report a series of novel C7-substituted coumarins, either synthesized or commercially purchased, which were identified as selective hMAO inhibitors. Most of the compounds demonstrated strong activities with IC50 values (half-inhibitory concentration) ranging from sub-micromolar to nanomolar. Compounds, FR1 and SP1, were identified as the most selective hMAO-A inhibitors, with IC50 values of 1.5 nM (selectivity index (SI) < −2.82) and 19 nM (SI < −2.42), respectively. FR4 and FR5 showed the most potent hMAO-B inhibitory activity, with IC50 of 18 nM and 15 nM (SI > 2.74 and SI > 2.82). Docking calculations and molecular dynamic simulations were performed to elucidate the selectivity preference and SAR profiles.


Sign in / Sign up

Export Citation Format

Share Document