scholarly journals Redesigning Vina@QNLM for Ultra-Large-Scale Molecular Docking and Screening on a Sunway Supercomputer

2021 ◽  
Vol 9 ◽  
Author(s):  
Hao Lu ◽  
Zhiqiang Wei ◽  
Cunji Wang ◽  
Jingjing Guo ◽  
Yuandong Zhou ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Large Scale ◽  
Management Process ◽  
Processor Architecture ◽  
Multicore Processor ◽  
Heterogeneous Multicore ◽  
Lead Compounds ◽  
Parallel Processes ◽  
Process Elements ◽  
Process Element

Ultra-large-scale molecular docking can improve the accuracy of lead compounds in drug discovery. In this study, we developed a molecular docking piece of software, Vina@QNLM, which can use more than 4,80,000 parallel processes to search for potential lead compounds from hundreds of millions of compounds. We proposed a task scheduling mechanism for large-scale parallelism based on Vinardo and Sunway supercomputer architecture. Then, we readopted the core docking algorithm to incorporate the full advantage of the heterogeneous multicore processor architecture in intensive computing. We successfully expanded it to 10, 465, 065 cores (1,61,001 management process elements and 0, 465, 065 computing process elements), with a strong scalability of 55.92%. To the best of our knowledge, this is the first time that 10 million cores are used for molecular docking on Sunway. The introduction of the heterogeneous multicore processor architecture achieved the best speedup, which is 11x more than that of the management process element of Sunway. The performance of Vina@QNLM was comprehensively evaluated using the CASF-2013 and CASF-2016 protein–ligand benchmarks, and the screening power was the highest out of the 27 pieces of software tested in the CASF-2013 benchmark. In some existing applications, we used Vina@QNLM to dock more than 10 million molecules to nine rigid proteins related to SARS-CoV-2 within 8.5 h on 10 million cores. We also developed a platform for the general public to use the software.

scholarly journals In Silico Prediction, Molecular Docking and Dynamics Studies of Steroidal Alkaloids of Holarrhena pubescens Wall. ex G. Don to Guanylyl Cyclase C: Implications in Designing of Novel Antidiarrheal Therapeutic Strategies

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4147
Author(s):  
Neha Gupta ◽  
Saurav Kumar Choudhary ◽  
Neeta Bhagat ◽  
Muthusamy Karthikeyan ◽  
Archana Chaturvedi
Keyword(s):  
Molecular Docking ◽  
Amino Acid ◽  
Guanylyl Cyclase ◽  
Extracellular Domain ◽  
Enterotoxigenic Escherichia Coli ◽  
Watery Diarrhea ◽  
Guanylyl Cyclase C ◽  
Amino Acid Residues ◽  
Lead Compounds

The binding of heat stable enterotoxin (STa) secreted by enterotoxigenic Escherichia coli (ETEC) to the extracellular domain of guanylyl cyclase c (ECDGC-C) causes activation of a signaling cascade, which ultimately results in watery diarrhea. We carried out this study with the objective of finding ligands that would interfere with the binding of STa on ECDGC-C. With this view in mind, we tested the biological activity of a alkaloid rich fraction of Holarrhena pubescens against ETEC under in vitro conditions. Since this fraction showed significant antibacterial activity against ETEC, we decided to test the screen binding affinity of nine compounds of steroidal alkaloid type from Holarrhena pubescens against extracellular domain (ECD) by molecular docking and identified three compounds with significant binding energy. Molecular dynamics simulations were performed for all the three lead compounds to establish the stability of their interaction with the target protein. Pharmacokinetics and toxicity profiling of these leads demonstrated that they possessed good drug-like properties. Furthermore, the ability of these leads to inhibit the binding of STa to ECD was evaluated. This was first done by identifying amino acid residues of ECDGC-C binding to STa by protein–protein docking. The results were matched with our molecular docking results. We report here that holadysenterine, one of the lead compounds that showed a strong affinity for the amino acid residues on ECDGC-C, also binds to STa. This suggests that holadysenterine has the potential to inhibit binding of STa on ECD and can be considered for future study, involving its validation through in vitro assays and animal model studies.

scholarly journals The AMBRE Project: r-process elements in the Milky Way thin and thick discs

2018 ◽  
Vol 619 ◽  
pp. A143 ◽  
Author(s):  
G. Guiglion ◽  
P. de Laverny ◽  
A. Recio-Blanco ◽  
N. Prantzos
Keyword(s):  
Chemical Evolution ◽  
Milky Way ◽  
Element Abundances ◽  
Thick Disc ◽  
Thin Disc ◽  
Solar Metallicity ◽  
R Process ◽  
Process Elements ◽  
Process Element ◽  
The Eu

Context. The chemical evolution of neutron capture elements in the Milky Way disc is still a matter of debate. There is a lack of statistically significant catalogues of such element abundances, especially those of the r-process. Aims. We aim to understand the chemical evolution of r-process elements in Milky Way disc. We focus on three pure r-process elements Eu, Gd, and Dy. We also consider a pure s-process element, Ba, in order to disentangle the different nucleosynthesis processes. Methods. We take advantage of high-resolution FEROS, HARPS, and UVES spectra from the ESO archive in order to perform a homogeneous analysis on 6500 FGK Milky Way stars. The chemical analysis is performed thanks to the automatic optimization pipeline GAUGUIN. We present abundances of Ba (5057 stars), Eu (6268 stars), Gd (5431 stars), and Dy (5479 stars). Based on the [α/Fe] ratio determined previously by the AMBRE Project, we chemically characterize the thin and the thick discs, and a metal-rich α-rich population. Results. First, we find that the [Eu/Fe] ratio follows a continuous sequence from the thin disc to the thick disc as a function of the metallicity. Second, in thick disc stars, the [Eu/Ba] ratio is found to be constant, while the [Gd/Ba] and [Dy/Ba] ratios decrease as a function of the metallicity. These observations clearly indicate a different nucleosynthesis history in the thick disc between Eu and Gd–Dy. The [r/Fe] ratio in the thin disc is roughly around +0.1 dex at solar metallicity, which is not the case for Ba. We also find that the α-rich metal-rich stars are also enriched in r-process elements (like thick disc stars), but their [Ba/Fe] is very different from thick disc stars. Finally, we find that the [r/α] ratio tends to decrease with metallicity, indicating that supernovae of different properties probably contribute differently to the synthesis of r-process elements and α-elements. Conclusions. We provide average abundance trends for [Ba/Fe] and [Eu/Fe] with rather small dispersions, and for the first time for [Gd/Fe] and [Dy/Fe]. This data may help to constrain chemical evolution models of Milky Way r- and s-process elements and the yields of massive stars. We emphasize that including yields of neutron-star or black hole mergers is now crucial if we want to quantitatively compare observations to Galactic chemical evolution models.

scholarly journals Exploiting the Reverse Vaccinology Approach to Design Novel Subunit Vaccine against Ebola Virus

2020 ◽  
Author(s):  
Md. Asad Ullah ◽  
Bishajit Sarkar ◽  
Syed Sajidul Islam
Keyword(s):  
Molecular Docking ◽  
Mhc Class Ii ◽  
Large Scale ◽  
Matrix Protein ◽  
Ebola Virus ◽  
Rna Virus ◽  
Docking Study ◽  
Dynamics Simulation ◽  
Molecular Docking Study ◽  
Class I Mhc

AbstractEbola virus is a highly pathogenic RNA virus that causes haemorrhagic fever in human. With very high mortality rate, Ebola virus is considered as one of the dangerous viruses in the world. Although, the Ebola outbreaks claimed many lives in the past, no satisfactory treatment or vaccine have been discovered yet to fight against Ebola. For this reason, in this study, various tools of bioinformatics and immunoinformatics were used to design possible vaccines against Zaire Ebola virus strain Mayinga-76. To construct the vaccine, three potential antigenic proteins of the virus, matrix protein VP40, envelope glycoprotein and nucleoprotein were selected against which the vaccines would be designed. The MHC class-I, MHC class-II and B-cell epitopes were determined and after robust analysis through various tools and molecular docking analysis, three vaccine candidates, designated as EV-1, EV-2 and EV-3, were constructed. Since the highly conserved epitopes were used for vaccine construction, these vaccine constructs are also expected to be effective on other strains of Ebola virus like strain Gabon-94 and Kikwit-95. Next, the molecular docking study on these vaccine constructs were analyzed by molecular docking study and EV-1 emerged as the best vaccine construct. Later, molecular dynamics simulation study revealed the good performances as well as good stability of the vaccine protein. Finally, codon adaptation and in silico cloning were conducted to design a possible plasmid (pET-19b plasmid vector was used) for large scale, industrial production of the EV-1 vaccine.

Applying Exogenous Humic Acids and Natural Zeolite for Remediating the Lead-Polluted Garden Soil

2010 ◽  
Vol 113-116 ◽  
pp. 919-922
Author(s):  
Wei Yu Shi ◽  
Hua Li ◽  
Li Ye Chu ◽  
Hong Bo Shao
Keyword(s):  
Humic Acids ◽  
Large Scale ◽  
Lead Concentration ◽  
Soluble Fraction ◽  
Water Soluble ◽  
Garden Soil ◽  
Polluted Soils ◽  
Lead Compounds ◽  
Mixed Treatment ◽  
The Difference

The study reported the co-remediation effect on the lead-polluted garden soil by zeolite and humic acids (HA), which was from comparing with the remediation of single zeolite in term of the lead fraction of sequential extraction in the soil and the distribution of lead in different parts of rape. Mixed treatment (zeolite and HA) and single treatment (zeolite) were, respectively, applied to the artificially polluted garden soil to examine the difference of their remediation effects in pot experiment. Results indicated that the co-remediation led to significantly greater (p < 0.01) reduction in the lead concentration in plants than by singly adding to zeolite. The co-application of zeolite and HA reduced the available fraction of lead compounds, but slightly increased (p < 0.01) the water-soluble fraction of lead compounds in the garden soil, compared with the application of single zeolite, especially in the severe lead-polluted soil (≥1000mg kg−1).This method might be an efficient way to remediate the lead-polluted soils on a large scale.

Applications of Molecular Docking

2016 ◽  
pp. 278-306
Author(s):  
Josephine Anthony ◽  
Vijaya Raghavan Rangamaran ◽  
Kumar T. Shivasankarasubbiah ◽  
Dharani Gopal ◽  
Kirubagaran Ramalingam
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Fatty Acid ◽  
Molecular Mechanisms ◽  
Fatty Acid Biosynthesis ◽  
Dynamics Simulation ◽  
Computational Techniques ◽  
Lead Compounds ◽  
Medical Interest ◽  
Insight Into

Computational tools have extended their reach into different realms of scientific research. Often coupled with molecular dynamics simulation, docking provides comprehensive insight into molecular mechanisms of biological processes. Influence of molecular docking is highly experienced in the field of structure based drug discovery, wherein docking is vital in validating novel lead compounds. The significance of molecular docking is also understood in several environmental and industrial research, in order to untangle the interactions among macromolecules of non-medical interest. Various processes such as bioremediation (REMEDIDOCK), nanomaterial interactions (NANODOCK), nutraceutical interactions (NUTRADOCK), fatty acid biosynthesis (FADOCK), and antifoulers interactions (FOULDOCK) find the application of molecular docking. This chapter emphasizes the involvement of computational techniques in the aforementioned fields to expand our knowledge on macromolecular interacting mechanisms.

Selecting a Photometric System for Gaia: C, N, O and Alpha-Process Elements

2003 ◽  
Vol 12 (4) ◽  
Author(s):  
G. Tautvaišienė ◽  
B. Edvardsson ◽  
S. Bartašiūtė
Keyword(s):  
Open Cluster ◽  
Stellar Atmospheres ◽  
Photometric System ◽  
Mixing Processes ◽  
Stellar Spectra ◽  
Element Abundances ◽  
Carbon And Nitrogen ◽  
Spectral Changes ◽  
Process Elements ◽  
Process Element

AbstractThe sensitivity of stellar spectra to C, N, O and α-process element abundances is discussed with the aim of taking this effect into account when selecting a photometric system for the Gaia orbiting observatory. On the basis of a spectrometric, photometric and theoretical study of spectra of evolved first-ascent giants and clump stars in the open cluster NGC 7789 it is demonstrated that evolutionary alterations of carbon and nitrogen abundances can cause noticeable spectral changes and, if not taken into account, may yield misleading photometric [Fe/H] determinations. Carbon features in stellar atmospheres show a particularly complex behavior being dependent on mixing processes in stars, on the stellar surface gravity and on the abundance of oxygen which can also be altered by different reasons. NH bands could serve for the evaluation of mixing processes in stars and the interpretation of carbon dominated spectral regions. Abundances of α-process elements can be evaluated photometrically by using the direct indicators - Ca II H and K lines and Mg I b triplet.

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