DOCSLIB.ORG

Methods and Applications of in Silico Aptamer Design and Modeling

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Methods and Applications of in Silico Aptamer Design and Modeling International Journal of Molecular Sciences Review Methods and Applications of In Silico Aptamer Design and Modeling Andrey A. Buglak 1,2,* , Alexey V. Samokhvalov 1 , Anatoly V. Zherdev 1 and Boris B. Dzantiev 1 1 A. N. Bach Institute of Biochemistry, Research Center of Biotechnology, Russian Academy of Sciences, Leninsky prospect 33, 119071 Moscow, Russia; [email protected] (A.V.S.); [email protected] (A.V.Z.); [email protected] (B.B.D.) 2 Physical Faculty, St. Petersburg State University, 7/9 Universitetskaya naberezhnaya, 199034 St. Petersburg, Russia * Correspondence: [email protected]; Tel.: +7-(495)-954-27-32 Received: 14 October 2020; Accepted: 8 November 2020; Published: 10 November 2020 Abstract: Aptamers are nucleic acid analogues of antibodies with high affinity to different targets, such as cells, viruses, proteins, inorganic materials, and coenzymes. Empirical approaches allow the design of in vitro aptamers that bind particularly to a target molecule with high affinity and selectivity. Theoretical methods allow significant expansion of the possibilities of aptamer design. In this study, we review theoretical and joint theoretical-experimental studies dedicated to aptamer design and modeling. We consider aptamers with different targets, such as proteins, antibiotics, organophosphates, nucleobases, amino acids, and drugs. During nucleic acid modeling and in silico design, a full set of in silico methods can be applied, such as docking, molecular dynamics (MD), and statistical analysis. The typical modeling workflow starts with structure prediction. Then, docking of target and aptamer is performed. Next, MD simulations are performed, which allows for an evaluation of the stability of aptamer/ligand complexes and determination of the binding energies with higher accuracy. Then, aptamer/ligand interactions are analyzed, and mutations of studied aptamers made. Subsequently, the whole procedure of molecular modeling can be reiterated. Thus, the interactions between aptamers and their ligands are complex and difficult to understand using only experimental approaches. Docking and MD are irreplaceable when aptamers are studied in silico. Keywords: aptamers; in silico design; molecular modeling; docking; molecular dynamics 1. Introduction Aptamers are single-stranded nucleic acids (both DNA and RNA) with a high affinity toward target molecules. In the past few years, aptamers have been obtained for a wide range of targets, for example, cells, viruses, inorganic materials, metal ions, coenzymes, nucleobases, amino acids, antibiotics, pesticides, polypeptides, and hormones and other low-molecular-weight molecules [1–3]. Multiple studies have been performed that are dedicated to the development of biosensors functionalized with aptamers; the biosensors are based on various nanomaterials: quantum dots, metal nanoparticles (NPs), and single- and multiwalled carbon nanotubes [4–6]. The systematic evolution of ligands by exponential enrichment, or SELEX, is an experimental method for the determination of nucleic acid aptamers that specifically bind to a target molecule with high affinity and selectivity [7]. The construction of aptamers using SELEX technology includes several rounds of selection and enrichment processes (Figure1), which are time and labor consuming and Int. J. Mol. Sci. 2020, 21, 8420; doi:10.3390/ijms21228420 www.mdpi.com/journal/ijms Int. J. Mol. Sci. 2020, 21, 8420 2 of 25 have a low cost-efficiency rate and output. SELEX may be combined with high-throughput sequencers, a process that is usually called HT-SELEX, or HTS [8,9]. Int. J. Mol. Sci. 2020, 21, x FOR PEER REVIEW 2 of 26 Figure 1. SchematicSchematic representation representation of SELEX aptamer selection and enrichment cycle. Currently, there are severalseveral varietiesvarieties ofof SELEXSELEX methodologiesmethodologies [[10].10]. Two Two major steps exist in aptamer design selection and optimization. In In the first first step, several polynucleotides with probable binding affinity affinity toward a target are screened by using thethe SELEXSELEX methodmethod andand thenthen selected.selected. In the second step, aptamers with detected high affinity affinity are shortened, modified,modified, and stabilized. Both DNA and RNA aptamers can be designed. The usage of noncanonical nucleotides is possible [[11].11]. An alternative strategy to SELEX that has been proposed in the past decade and a half is to apply computational computational methods methods of of bioinformatics, bioinformatics, namely, namely, docking docking and and molecular molecular dynamics dynamics (MD), (MD), to designto design aptamers aptamers for for various various purp purposes.oses. Of Of course, course, the the in in silico silico approach approach can can be be used used along with SELEX and HTSHTS toto raiseraise thethe eefficacyfficacy of of research. research. Some Some in in silico silico tools tools are are specialized specialized for for the the analysis analysis of ofHTS HTS experimental experimental data data [12]. [12]. Rapid Rapid expansion expansion and integrationand integration of next-generation of next-generation sequencing sequencing (NGS) (NGS)opens theopens possibility the possibility for conducting for conducting new high-throughput new high-throughput experiments experiments and developing and developing new screening new screeningstrategies [strategies13]. [13]. Hamada [14[14]] highlighted highlighted several several methods methods of oligonucleotide of oligonucleotide aptamer aptamer design: scalabledesign: clustering scalable clusteringfor RNA aptamers for RNA and aptamers motif-finding and motif-finding methods as wellmeth asods aptamer as well optimization as aptamer methods.optimization An up-to-date methods. Anreview up-to-date of aptamer review design of aptamer software design is summarized software is in summarized the paper by in Emamithe paper et al.by[ 15Emami]. Additionally, et al. [15]. Additionally,new scoring functions new scoring are beingfunctions developed, are being such developed, as that in such the studyas that by in Yanthe study and Wang by Yan [16 and]. In Wang silico [16].aptamer In silico design aptamer is usually design performed is usually with docking performed and MD.with Sometimes, docking and empirical MD. Sometimes, research is carriedempirical out withresearch only is one carried technique, out with for example,only one technique, MD. Sometimes, for example, MD of oligonucleotideMD. Sometimes, aptamers MD of oligonucleotide is accompanied aptamersby hybrid is quantumaccompanied mechanics by hybrid/molecular quantum mechanics mechanics/molecular (QM/MM) studies mechanics [17]. (QM/MM) The quantitative studies [17].structure–activity The quantitative relationship structure–activity (QSAR) methodrelationsh canip be(QSAR) used alongmethod with can other be used molecular along with modeling other molecularmethods for modeling aptamer methods design [18 for]. Thus,aptame ar full design set of [18]. molecular Thus, a modeling full set of in molecular silico tools modeling can be exploited in silico toolsfor aptamer can be design.exploited Moreover, for aptame mathematicalr design. Moreover, modeling mathematical of ligand/aptamer modeling interaction of ligand/aptamer kinetics is interactionfeasible [19 ,kinetics20]. is feasible [19,20]. A riboswitch is a noncoding RNA (ncRNA) that performs the function of of genetic genetic “switching” “switching” and regulates gene expression in response to a spec specificific molecular target. Riboswitches are regulatory RNA components, which are usually located in the 5′-untranslated region of certain mRNAs and control gene expression during transcription or translation. These components consist of a sensor domain and a neighboring actuator domain. The sensor domain is an aptamer that specifically binds to a ligand, and the actuator domain includes an intrinsic terminator or a ribosomal binding site for Int. J. Mol. Sci. 2020, 21, 8420 3 of 25 RNA components, which are usually located in the 50-untranslated region of certain mRNAs and control gene expression during transcription or translation. These components consist of a sensor domainInt. J. Mol. and Sci. 2020 a neighboring, 21, x FOR PEER actuator REVIEW domain. The sensor domain is an aptamer that specifically binds3 of 26 to a ligand, and the actuator domain includes an intrinsic terminator or a ribosomal binding site for transcriptionaltranscriptional or or translational translational regulation, regulation, respectively. respectively. A A large large part part of of the the research research dedicated dedicated to to the the designdesign of of oligonucleotide oligonucleotide aptamers aptamers belongs belongs to to the the development development of of RNA RNA riboswitches riboswitches [ 21[21–25].–25]. InIn silico silico tools tools provide provide a a wide wide range range of of methods methods to to a a researcher. researcher. It It is is possible possible to to design design aptamers aptamers usingusing simplesimple compoundscompounds asas targetstargets as as well well as as complex complex biopolymers, biopolymers, such such as as proteins. proteins. TheThe singlesingle disadvantagedisadvantage isis thatthat thethe currentcurrent levellevel ofof molecularmolecular modelingmodeling makesmakes itit impossibleimpossible toto useuse cellscells asas targetstargets in in aptamer aptamer design, design, which which is is a a plus plus of of the thein in vitro vitroSELEX SELEX method. method. Using Using molecular molecular modeling
Load more

Recommended publications
  • Pyplif HIPPOS-Assisted Prediction of Molecular Determinants of Ligand Binding to Receptors
    molecules Article PyPLIF HIPPOS-Assisted Prediction of Molecular Determinants of Ligand Binding to Receptors Enade P. Istyastono 1,* , Nunung Yuniarti 2, Vivitri D. Prasasty 3 and Sudi Mungkasi 4 1 Faculty of Pharmacy, Sanata Dharma University, Yogyakarta 55282, Indonesia 2 Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta 55281, Indonesia; [email protected] 3 Faculty of Biotechnology, Atma Jaya Catholic University of Indonesia, Jakarta 12930, Indonesia; [email protected] 4 Department of Mathematics, Faculty of Science and Technology, Sanata Dharma University, Yogyakarta 55282, Indonesia; [email protected] * Correspondence: [email protected]; Tel.: +62-274883037 Abstract: Identification of molecular determinants of receptor-ligand binding could significantly increase the quality of structure-based virtual screening protocols. In turn, drug design process, especially the fragment-based approaches, could benefit from the knowledge. Retrospective virtual screening campaigns by employing AutoDock Vina followed by protein-ligand interaction finger- printing (PLIF) identification by using recently published PyPLIF HIPPOS were the main techniques used here. The ligands and decoys datasets from the enhanced version of the database of useful de- coys (DUDE) targeting human G protein-coupled receptors (GPCRs) were employed in this research since the mutation data are available and could be used to retrospectively verify the prediction. The results show that the method presented in this article could pinpoint some retrospectively verified molecular determinants. The method is therefore suggested to be employed as a routine in drug Citation: Istyastono, E.P.; Yuniarti, design and discovery. N.; Prasasty, V.D.; Mungkasi, S. PyPLIF HIPPOS-Assisted Prediction Keywords: PyPLIF HIPPOS; AutoDock Vina; drug discovery; fragment-based; molecular determi- of Molecular Determinants of Ligand Binding to Receptors.
    [Show full text]
  • Open Babel Documentation Release 2.3.1
    Open Babel Documentation Release 2.3.1 Geoffrey R Hutchison Chris Morley Craig James Chris Swain Hans De Winter Tim Vandermeersch Noel M O’Boyle (Ed.) December 05, 2011 Contents 1 Introduction 3 1.1 Goals of the Open Babel project ..................................... 3 1.2 Frequently Asked Questions ....................................... 4 1.3 Thanks .................................................. 7 2 Install Open Babel 9 2.1 Install a binary package ......................................... 9 2.2 Compiling Open Babel .......................................... 9 3 obabel and babel - Convert, Filter and Manipulate Chemical Data 17 3.1 Synopsis ................................................. 17 3.2 Options .................................................. 17 3.3 Examples ................................................. 19 3.4 Differences between babel and obabel .................................. 21 3.5 Format Options .............................................. 22 3.6 Append property values to the title .................................... 22 3.7 Filtering molecules from a multimolecule file .............................. 22 3.8 Substructure and similarity searching .................................. 25 3.9 Sorting molecules ............................................ 25 3.10 Remove duplicate molecules ....................................... 25 3.11 Aliases for chemical groups ....................................... 26 4 The Open Babel GUI 29 4.1 Basic operation .............................................. 29 4.2 Options .................................................
    [Show full text]
  • Real-Time Pymol Visualization for Rosetta and Pyrosetta
    Real-Time PyMOL Visualization for Rosetta and PyRosetta Evan H. Baugh1, Sergey Lyskov1, Brian D. Weitzner1, Jeffrey J. Gray1,2* 1 Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland, United States of America, 2 Program in Molecular Biophysics, The Johns Hopkins University, Baltimore, Maryland, United States of America Abstract Computational structure prediction and design of proteins and protein-protein complexes have long been inaccessible to those not directly involved in the field. A key missing component has been the ability to visualize the progress of calculations to better understand them. Rosetta is one simulation suite that would benefit from a robust real-time visualization solution. Several tools exist for the sole purpose of visualizing biomolecules; one of the most popular tools, PyMOL (Schro¨dinger), is a powerful, highly extensible, user friendly, and attractive package. Integrating Rosetta and PyMOL directly has many technical and logistical obstacles inhibiting usage. To circumvent these issues, we developed a novel solution based on transmitting biomolecular structure and energy information via UDP sockets. Rosetta and PyMOL run as separate processes, thereby avoiding many technical obstacles while visualizing information on-demand in real-time. When Rosetta detects changes in the structure of a protein, new coordinates are sent over a UDP network socket to a PyMOL instance running a UDP socket listener. PyMOL then interprets and displays the molecule. This implementation also allows remote execution of Rosetta. When combined with PyRosetta, this visualization solution provides an interactive environment for protein structure prediction and design. Citation: Baugh EH, Lyskov S, Weitzner BD, Gray JJ (2011) Real-Time PyMOL Visualization for Rosetta and PyRosetta.
    [Show full text]
  • Molecular Dynamics Simulations in Drug Discovery and Pharmaceutical Development
    processes Review Molecular Dynamics Simulations in Drug Discovery and Pharmaceutical Development Outi M. H. Salo-Ahen 1,2,* , Ida Alanko 1,2, Rajendra Bhadane 1,2 , Alexandre M. J. J. Bonvin 3,* , Rodrigo Vargas Honorato 3, Shakhawath Hossain 4 , André H. Juffer 5 , Aleksei Kabedev 4, Maija Lahtela-Kakkonen 6, Anders Støttrup Larsen 7, Eveline Lescrinier 8 , Parthiban Marimuthu 1,2 , Muhammad Usman Mirza 8 , Ghulam Mustafa 9, Ariane Nunes-Alves 10,11,* , Tatu Pantsar 6,12, Atefeh Saadabadi 1,2 , Kalaimathy Singaravelu 13 and Michiel Vanmeert 8 1 Pharmaceutical Sciences Laboratory (Pharmacy), Åbo Akademi University, Tykistökatu 6 A, Biocity, FI-20520 Turku, Finland; ida.alanko@abo.fi (I.A.); rajendra.bhadane@abo.fi (R.B.); parthiban.marimuthu@abo.fi (P.M.); atefeh.saadabadi@abo.fi (A.S.) 2 Structural Bioinformatics Laboratory (Biochemistry), Åbo Akademi University, Tykistökatu 6 A, Biocity, FI-20520 Turku, Finland 3 Faculty of Science-Chemistry, Bijvoet Center for Biomolecular Research, Utrecht University, 3584 CH Utrecht, The Netherlands; [email protected] 4 Swedish Drug Delivery Forum (SDDF), Department of Pharmacy, Uppsala Biomedical Center, Uppsala University, 751 23 Uppsala, Sweden; [email protected] (S.H.); [email protected] (A.K.) 5 Biocenter Oulu & Faculty of Biochemistry and Molecular Medicine, University of Oulu, Aapistie 7 A, FI-90014 Oulu, Finland; andre.juffer@oulu.fi 6 School of Pharmacy, University of Eastern Finland, FI-70210 Kuopio, Finland; maija.lahtela-kakkonen@uef.fi (M.L.-K.); tatu.pantsar@uef.fi
    [Show full text]
  • Ee9e60701e814784783a672a9
    International Journal of Technology (2017) 4: 611‐621 ISSN 2086‐9614 © IJTech 2017 A PRELIMINARY STUDY ON SHIFTING FROM VIRTUAL MACHINE TO DOCKER CONTAINER FOR INSILICO DRUG DISCOVERY IN THE CLOUD Agung Putra Pasaribu1, Muhammad Fajar Siddiq1, Muhammad Irfan Fadhila1, Muhammad H. Hilman1, Arry Yanuar2, Heru Suhartanto1* 1Faculty of Computer Science, Universitas Indonesia, Kampus UI Depok, Depok 16424, Indonesia 2Faculty of Pharmacy, Universitas Indonesia, Kampus UI Depok, Depok 16424, Indonesia (Received: January 2017 / Revised: April 2017 / Accepted: June 2017) ABSTRACT The rapid growth of information technology and internet access has moved many offline activities online. Cloud computing is an easy and inexpensive solution, as supported by virtualization servers that allow easier access to personal computing resources. Unfortunately, current virtualization technology has some major disadvantages that can lead to suboptimal server performance. As a result, some companies have begun to move from virtual machines to containers. While containers are not new technology, their use has increased recently due to the Docker container platform product. Docker’s features can provide easier solutions. In this work, insilico drug discovery applications from molecular modelling to virtual screening were tested to run in Docker. The results are very promising, as Docker beat the virtual machine in most tests and reduced the performance gap that exists when using a virtual machine (VirtualBox). The virtual machine placed third in test performance, after the host itself and Docker. Keywords: Cloud computing; Docker container; Molecular modeling; Virtual screening 1. INTRODUCTION In recent years, cloud computing has entered the realm of information technology (IT) and has been widely used by the enterprise in support of business activities (Foundation, 2016).
    [Show full text]
  • An Explicit-Solvent Conformation Search Method Using Open Software
    An explicit-solvent conformation search method using open software Kari Gaalswyk and Christopher N. Rowley Department of Chemistry, Memorial University of Newfoundland, St. John’s, Newfoundland and Labrador, Canada ABSTRACT Computer modeling is a popular tool to identify the most-probable conformers of a molecule. Although the solvent can have a large effect on the stability of a conformation, many popular conformational search methods are only capable of describing molecules in the gas phase or with an implicit solvent model. We have developed a work-flow for performing a conformation search on explicitly-solvated molecules using open source software. This method uses replica exchange molecular dynamics (REMD) to sample the conformational states of the molecule efficiently. Cluster analysis is used to identify the most probable conformations from the simulated trajectory. This work-flow was tested on drug molecules a-amanitin and cabergoline to illustrate its capabilities and effectiveness. The preferred conformations of these molecules in gas phase, implicit solvent, and explicit solvent are significantly different. Subjects Biophysics, Pharmacology, Computational Science Keywords Conformation search, Explicit solvent, Cluster analysis, Replica exchange molecular dynamics INTRODUCTION Many molecules can exist in multiple conformational isomers. Conformational isomers have the same chemical bonds, but differ in their 3D geometry because they hold different torsional angles (Crippen & Havel, 1988). The conformation of a molecule can affect Submitted 5 April 2016 chemical reactivity, molecular binding, and biological activity (Struthers, Rivier & Accepted 6May2016 Published 31 May 2016 Hagler, 1985; Copeland, 2011). Conformations differ in stability because they experience different steric, electrostatic, and solute-solvent interactions. The probability, p,ofa Corresponding author Christopher N.
    [Show full text]
  • Evaluation of Protein-Ligand Docking Methods on Peptide-Ligand
    bioRxiv preprint doi: https://doi.org/10.1101/212514; this version posted November 1, 2017. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Evaluation of protein-ligand docking methods on peptide-ligand complexes for docking small ligands to peptides Sandeep Singh1#, Hemant Kumar Srivastava1#, Gaurav Kishor1#, Harinder Singh1, Piyush Agrawal1 and G.P.S. Raghava1,2* 1CSIR-Institute of Microbial Technology, Sector 39A, Chandigarh, India. 2Indraprastha Institute of Information Technology, Okhla Phase III, Delhi India #Authors Contributed Equally Emails of Authors: SS: [email protected] HKS: [email protected] GK: [email protected] HS: [email protected] PA: [email protected] * Corresponding author Professor of Center for Computation Biology, Indraprastha Institute of Information Technology (IIIT Delhi), Okhla Phase III, New Delhi-110020, India Phone: +91-172-26907444 Fax: +91-172-26907410 E-mail: [email protected] Running Title: Benchmarking of docking methods 1 bioRxiv preprint doi: https://doi.org/10.1101/212514; this version posted November 1, 2017. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. ABSTRACT In the past, many benchmarking studies have been performed on protein-protein and protein-ligand docking however there is no study on peptide-ligand docking.
    [Show full text]
  • Python Tools in Computational Chemistry (And Biology)
    Python Tools in Computational Chemistry (and Biology) Andrew Dalke Dalke Scientific, AB Göteborg, Sweden EuroSciPy, 26-27 July, 2008 “Why does ‘import numpy’ take 0.4 seconds? Does it need to import 228 libraries?” - My first Numpy-discussion post (paraphrased) Your use case isn't so typical and so suffers on the import time end of the balance. - Response from Robert Kern (Others did complain. Import time down to 0.28s.) 52,000 structures PDB doubles every 2½ years HEADER PHOTORECEPTOR 23-MAY-90 1BRD 1BRD 2 COMPND BACTERIORHODOPSIN 1BRD 3 SOURCE (HALOBACTERIUM $HALOBIUM) 1BRD 4 EXPDTA ELECTRON DIFFRACTION 1BRD 5 AUTHOR R.HENDERSON,J.M.BALDWIN,T.A.CESKA,F.ZEMLIN,E.BECKMANN, 1BRD 6 AUTHOR 2 K.H.DOWNING 1BRD 7 REVDAT 3 15-JAN-93 1BRDB 1 SEQRES 1BRDB 1 REVDAT 2 15-JUL-91 1BRDA 1 REMARK 1BRDA 1 .. ATOM 54 N PRO 8 20.397 -15.569 -13.739 1.00 20.00 1BRD 136 ATOM 55 CA PRO 8 21.592 -15.444 -12.900 1.00 20.00 1BRD 137 ATOM 56 C PRO 8 21.359 -15.206 -11.424 1.00 20.00 1BRD 138 ATOM 57 O PRO 8 21.904 -15.930 -10.563 1.00 20.00 1BRD 139 ATOM 58 CB PRO 8 22.367 -14.319 -13.591 1.00 20.00 1BRD 140 ATOM 59 CG PRO 8 22.089 -14.564 -15.053 1.00 20.00 1BRD 141 ATOM 60 CD PRO 8 20.647 -15.054 -15.103 1.00 20.00 1BRD 142 ATOM 61 N GLU 9 20.562 -14.211 -11.095 1.00 20.00 1BRD 143 ATOM 62 CA GLU 9 20.192 -13.808 -9.737 1.00 20.00 1BRD 144 ATOM 63 C GLU 9 19.567 -14.935 -8.932 1.00 20.00 1BRD 145 ATOM 64 O GLU 9 19.815 -15.104 -7.724 1.00 20.00 1BRD 146 ATOM 65 CB GLU 9 19.248 -12.591 -9.820 1.00 99.00 1 1BRD 147 ATOM 66 CG GLU 9 19.902 -11.351 -10.387 1.00 99.00 1 1BRD 148 ATOM 67 CD GLU 9 19.243 -10.169 -10.980 1.00 99.00 1 1BRD 149 ATOM 68 OE1 GLU 9 18.323 -10.191 -11.782 1.00 99.00 1 1BRD 150 ATOM 69 OE2 GLU 9 19.760 -9.089 -10.597 1.00 99.00 1 1BRD 151 ATOM 70 N TRP 10 18.764 -15.737 -9.597 1.00 20.00 1BRD 152 ATOM 71 CA TRP 10 18.034 -16.884 -9.090 1.00 20.00 1BRD 153 ATOM 72 C TRP 10 18.843 -17.908 -8.318 1.00 20.00 1BRD 154 ATOM 73 O TRP 10 18.376 -18.310 -7.230 1.00 20.00 1BRD 155 .
    [Show full text]
  • In Silico Screening and Molecular Docking of Bioactive Agents Towards Human Coronavirus Receptor
    GSC Biological and Pharmaceutical Sciences, 2020, 11(01), 132–140 Available online at GSC Online Press Directory GSC Biological and Pharmaceutical Sciences e-ISSN: 2581-3250, CODEN (USA): GBPSC2 Journal homepage: https://www.gsconlinepress.com/journals/gscbps (RESEARCH ARTICLE) In silico screening and molecular docking of bioactive agents towards human coronavirus receptor Pratyush Kumar *, Asnani Alpana, Chaple Dinesh and Bais Abhinav Priyadarshini J. L. College of Pharmacy, Electronic Building, Electronic Zone, MIDC, Hingna Road, Nagpur-440016, Maharashtra, India. Publication history: Received on 09 April 2020; revised on 13 April 2020; accepted on 15 April 2020 Article DOI: https://doi.org/10.30574/gscbps.2020.11.1.0099 Abstract Coronavirus infection has turned into pandemic despite of efforts of efforts of countries like America, Italy, China, France etc. Currently India is also outraged by the virulent effect of coronavirus. Although World Health Organisation initially claimed to have all controls over the virus, till date infection has coasted several lives worldwide. Currently we do not have enough time for carrying out traditional approaches of drug discovery. Computer aided drug designing approaches are the best solution. The present study is completely dedicated to in silico approaches like virtual screening, molecular docking and molecular property calculation. The library of 15 bioactive molecules was built and virtual screening was carried towards the crystalline structure of human coronavirus (6nzk) which was downloaded from protein database. Pyrx virtual screening tool was used and results revealed that F14 showed best binding affinity. The best screened molecule was further allowed to dock with the target using Autodock vina software.
    [Show full text]
  • In Silico Tools for Splicing Defect Prediction: a Survey from the Viewpoint of End Users
    © American College of Medical Genetics and Genomics REVIEW In silico tools for splicing defect prediction: a survey from the viewpoint of end users Xueqiu Jian, MPH1, Eric Boerwinkle, PhD1,2 and Xiaoming Liu, PhD1 RNA splicing is the process during which introns are excised and informaticians in relevant areas who are working on huge data sets exons are spliced. The precise recognition of splicing signals is critical may also benefit from this review. Specifically, we focus on those tools to this process, and mutations affecting splicing comprise a consider- whose primary goal is to predict the impact of mutations within the able proportion of genetic disease etiology. Analysis of RNA samples 5′ and 3′ splicing consensus regions: the algorithms used by different from the patient is the most straightforward and reliable method to tools as well as their major advantages and disadvantages are briefly detect splicing defects. However, currently, the technical limitation introduced; the formats of their input and output are summarized; prohibits its use in routine clinical practice. In silico tools that predict and the interpretation, evaluation, and prospection are also discussed. potential consequences of splicing mutations may be useful in daily Genet Med advance online publication 21 November 2013 diagnostic activities. In this review, we provide medical geneticists with some basic insights into some of the most popular in silico tools Key Words: bioinformatics; end user; in silico prediction tool; for splicing defect prediction, from the viewpoint of end users. Bio- medical genetics; splicing consensus region; splicing mutation INTRODUCTION TO PRE-mRNA SPLICING AND small nuclear ribonucleoproteins and more than 150 proteins, MUTATIONS AFFECTING SPLICING serine/arginine-rich (SR) proteins, heterogeneous nuclear ribo- Sixty years ago, the milestone discovery of the double-helix nucleoproteins, and the regulatory complex (Figure 1).
    [Show full text]
  • 64-194 Projekt Parallelrechnerevaluation Abschlussbericht
    64-194 Projekt Parallelrechnerevaluation Abschlussbericht Automatisierte Build-Tests für Spack Sarah Lubitz Malte Fock [email protected] [email protected] Studiengang: LA Berufliche Schulen – Informatik Studiengang LaGym - Informatik Matr.-Nr. 6570465 Matr.-Nr. 6311966 Inhaltsverzeichnis i Inhaltsverzeichnis 1 Einleitung1 1.1 Motivation.....................................1 1.2 Vorbereitungen..................................2 1.2.1 Spack....................................2 1.2.2 Python...................................2 1.2.3 Unix-Shell.................................3 1.2.4 Slurm....................................3 1.2.5 GitHub...................................4 2 Code 7 2.1 Automatisiertes Abrufen und Installieren von Spack-Paketen.......7 2.1.1 Python Skript: install_all_packets.py..................7 2.2 Batch-Jobskripte..................................9 2.2.1 Test mit drei Paketen........................... 10 2.3 Analyseskript................................... 11 2.3.1 Test mit 500 Paketen........................... 12 2.3.2 Code zur Analyse der Error-Logs, forts................. 13 2.4 Hintereinanderausführung der Installationen................. 17 2.4.1 Wrapper Skript.............................. 19 2.5 E-Mail Benachrichtigungen........................... 22 3 Testlauf 23 3.1 Durchführung und Ergebnisse......................... 23 3.2 Auswertung und Schlussfolgerungen..................... 23 3.3 Fazit und Ausblick................................ 24 4 Schulische Relevanz 27 Literaturverzeichnis
    [Show full text]
  • How to Print a Crystal Structure Model in 3D Teng-Hao Chen,*A Semin Lee, B Amar H
    Electronic Supplementary Material (ESI) for CrystEngComm. This journal is © The Royal Society of Chemistry 2014 How to Print a Crystal Structure Model in 3D Teng-Hao Chen,*a Semin Lee, b Amar H. Flood b and Ognjen Š. Miljanić a a Department of Chemistry, University of Houston, 112 Fleming Building, Houston, Texas 77204-5003, United States b Department of Chemistry, Indiana University, 800 E. Kirkwood Avenue, Bloomington, Indiana 47405, United States Supporting Information Instructions for Printing a 3D Model of an Interlocked Molecule: Cyanostars .................................... S2 Instructions for Printing a "Molecular Spinning Top" in 3D: Triazolophanes ..................................... S3 References ....................................................................................................................................................................... S4 S1 Instructions for Printing a 3D Model of an Interlocked Molecule: Cyanostars Mechanically interlocked molecules such as rotaxanes and catenanes can also be easily printed in 3D. As long as the molecule is correctly designed and modeled, there is no need to assemble and glue the components after printing—they are printed inherently as mechanically interlocked molecules. We present the preparation of a cyanostar- based [3]rotaxane as an example. A pair of sandwiched cyanostars S1 (CS ) derived from the crystal structure was "cleaned up" in the molecular computation software Spartan ʹ10, i.e. disordered atoms were removed. A linear molecule was created and threaded through the cavity of two cyanostars (Figure S1a). Using a space filling view of the molecule, the three components were spaced sufficiently far apart to ensure that they did not make direct contact Figure S1 . ( a) Side and top view of two cyanostars ( CS ) with each other when they are printed. threaded with a linear molecule. ( b) Side and top view of a Bulky stoppers were added to each [3]rotaxane.
    [Show full text]