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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. -
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 ................................................. -
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 -
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). -
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. -
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. -
Homology Modeling, Virtual Screening, Prime- MMGBSA, Autodock-Identification of Inhibitors of FGR Protein
Article Volume 11, Issue 4, 2021, 11088 - 11103 https://doi.org/10.33263/BRIAC114.1108811103 Homology Modeling, Virtual Screening, Prime- MMGBSA, AutoDock-Identification of Inhibitors of FGR Protein Narasimha Muddagoni 1 , Revanth Bathula 1 , Mahender Dasari 1 , Sarita Rajender Potlapally 1,* 1 Molecular Modeling Laboratory, Department of Chemistry, Nizam College, Osmania University, Hyderabad, India; * Correspondence: [email protected], [email protected]; Scopus Author ID 55317928000 Received: 11.11.2020; Revised: 4.12.2020; Accepted: 5.12.2020; Published: 8.12.2020 Abstract: Carcinogenesis is a multi-stage process in which damage to a cell's genetic material changes the cell from normal to malignant. Tyrosine-protein kinase FGR is a protein, member of the Src family kinases (SFks), nonreceptor tyrosine kinases involved in regulating various signaling pathways that promote cell proliferation and migration. FGR protein is also called Gardner-Rasheed Feline Sarcoma viral (v-fgr) oncogene homolog. FGR, FGR protein has an aberrant expression upregulated and activated by the tumor necrosis factor activation (TNF), enhancing the activity of FGR by phosphorylation and activation, causing ovarian cancer. In the present study, 3D structure of FGR protein is built by using comparative homology modeling techniques using MODELLER9.9 program. Energy minimization of protein is done by NAMD-VMD software. The quality of the protein is evaluated with ProSA, Verify 3D and Ramchandran Plot validated tools. The active site of protein is generated using SiteMap and literature Studies. In the present study of research, FGR protein was subjected to virtual screening with TOSLab ligand molecules database in the Schrodinger suite, to result in 12 lead molecules prioritized based on docking score, binding free energy and ADME properties. -
Hands-On Tutorials of Autodock 4 and Autodock Vina
Hands-on tutorials of AutoDock 4 and AutoDock Vina Pei-Ying Chu (朱珮瑩) Supervisor: Jung-Hsin Lin (林榮信) Research Center for Applied Sciences, Academia Sinica 2018 Frontiers in Computational Drug Design, Academia Sinica, March 16-20, 2018 AutoDock http://autodock.scripps.edu AutoDock is a suite of automated docking tools. It is designed to predict how small molecules, such as substrates or drug candidates, bind to a receptor of known 3D structure. AutoDock 4 is free and is available under the GNU General Public License. 2 AutoDock Vina http://vina.scripps.edu/ Because the scoring functions used by AutoDock 4 and AutoDock Vina are different and inexact, on any given problem, either program may provide a better result. AutoDock Vina is available under the Apache license, allowing commercial and 3 non-commercial use and redistribution. http://autodock.scripps.edu/downloads These programs were installed on VM. 4 http://mgltools.scripps.edu/ AutoDockTools (ADT) is developed to help set up the docking. ADT is included in MGLTools packages. 5 In general, each docking (AutoDock 4 and/or AutoDock Vina) requires: 1. structure of the receptor (protein), in pdbqt format 2. structure of the ligand (small molecule, drug, etc.) in pdbqt format 3. docking and grid parameters (search space) PDBQT format is very similar to PDB format but it includes partial charges ('Q') and AutoDock 4 (AD4) atom types ('T'). • Preparing the ligand involves ensuring that its atoms are assigned the correct AutoDock4 atom types, adding Gasteiger charges if necessary, merging non-polar hydrogens, detecting aromatic carbons if any, and setting up the 'torsion tree'. -
Dockomatic - Automated Ligand Creation and Docking Casey W
Boise State University ScholarWorks Chemistry Faculty Publications and Presentations Department of Chemistry and Biochemistry 11-8-2010 DockoMatic - Automated Ligand Creation and Docking Casey W. Bullock Boise State University Reed B. Jacob Boise State University Owen M. McDougal Boise State University Greg Hampikian Boise State University Tim Andersen Boise State University This document was originally published by BioMed Central in BMC Research Notes. Copyright restrictions may apply. DOI: 10.1186/ 1756-0500-3-289 DockoMatic - Automated Ligand Creation and Docking Casey W. Bullock1, Reed B. Jacob2, Owen M. McDougal3, Greg Hampikian4, Tim Andersen∗5 1;5Computer Science Department, Boise State University, Boise, Idaho 83725, USA 2;3Department of Chemistry and Biochemistry, Boise State University, Boise, Idaho 83725, USA 4Department of Biological Sciences, Boise State University, Boise, Idaho 83725, USA Email: Casey W. Bullock - [email protected]; Reed B. Jacob - [email protected]; Owen M. McDougal - [email protected]; Greg Hampikian - [email protected]; Tim Andersen∗- [email protected]; ∗Corresponding author Abstract Background: The application of computational modeling to rationally design drugs and characterize macro biomolecular receptors has proven increasingly useful due to the accessibility of computing clusters and clouds. AutoDock is a well-known and powerful software program used to model ligand to receptor binding interactions. In its current version, AutoDock requires significant amounts of user time to setup and run jobs, and collect results. This paper presents DockoMatic, a user friendly Graphical User Interface (GUI) application that eases and automates the creation and management of AutoDock jobs for high throughput screening of ligand to receptor interactions. -
Computational Evidence for Nitro Derivatives of Quinoline and Quinoline N‑Oxide As Low‑Cost Alternative for the Treatment of SARS‑Cov‑2 Infection Letícia C
www.nature.com/scientificreports OPEN Computational evidence for nitro derivatives of quinoline and quinoline N‑oxide as low‑cost alternative for the treatment of SARS‑CoV‑2 infection Letícia C. Assis1, Alexandre A. de Castro1, João P. A. de Jesus2, Eugenie Nepovimova3, Kamil Kuca3*, Teodorico C. Ramalho1,3 & Felipe A. La Porta2* A new and more aggressive strain of coronavirus, known as SARS‑CoV‑2, which is highly contagious, has rapidly spread across the planet within a short period of time. Due to its high transmission rate and the signifcant time–space between infection and manifestation of symptoms, the WHO recently declared this a pandemic. Because of the exponentially growing number of new cases of both infections and deaths, development of new therapeutic options to help fght this pandemic is urgently needed. The target molecules of this study were the nitro derivatives of quinoline and quinoline N‑oxide. Computational design at the DFT level, docking studies, and molecular dynamics methods as a well‑reasoned strategy will aid in elucidating the fundamental physicochemical properties and molecular functions of a diversity of compounds, directly accelerating the process of discovering new drugs. In this study, we discovered isomers based on the nitro derivatives of quinoline and quinoline N‑oxide, which are biologically active compounds and may be low‑cost alternatives for the treatment of infections induced by SARS‑CoV‑2. We are currently facing a new coronavirus disease designated as COVID-19. It started in China and has spread rapidly around the world, resulting in serious threats to international health and the economy1,2. -
Application of Various Molecular Modelling Methods in the Study of Estrogens and Xenoestrogens
International Journal of Molecular Sciences Review Application of Various Molecular Modelling Methods in the Study of Estrogens and Xenoestrogens Anna Helena Mazurek 1 , Łukasz Szeleszczuk 1,* , Thomas Simonson 2 and Dariusz Maciej Pisklak 1 1 Chair and Department of Physical Pharmacy and Bioanalysis, Department of Physical Chemistry, Medical Faculty of Pharmacy, University of Warsaw, Banacha 1 str., 02-093 Warsaw Poland; [email protected] (A.H.M.); [email protected] (D.M.P.) 2 Laboratoire de Biochimie (CNRS UMR7654), Ecole Polytechnique, 91-120 Palaiseau, France; [email protected] * Correspondence: [email protected]; Tel.: +48-501-255-121 Received: 21 July 2020; Accepted: 1 September 2020; Published: 3 September 2020 Abstract: In this review, applications of various molecular modelling methods in the study of estrogens and xenoestrogens are summarized. Selected biomolecules that are the most commonly chosen as molecular modelling objects in this field are presented. In most of the reviewed works, ligand docking using solely force field methods was performed, employing various molecular targets involved in metabolism and action of estrogens. Other molecular modelling methods such as molecular dynamics and combined quantum mechanics with molecular mechanics have also been successfully used to predict the properties of estrogens and xenoestrogens. Among published works, a great number also focused on the application of different types of quantitative structure–activity relationship (QSAR) analyses to examine estrogen’s structures and activities. Although the interactions between estrogens and xenoestrogens with various proteins are the most commonly studied, other aspects such as penetration of estrogens through lipid bilayers or their ability to adsorb on different materials are also explored using theoretical calculations. -
Chem3d 17.0 User Guide Chem3d 17.0
Chem3D 17.0 User Guide Chem3D 17.0 Table of Contents Recent Additions viii Chapter 1: About Chem3D 1 Additional computational engines 1 Serial numbers and technical support 3 About Chem3D Tutorials 3 Chapter 2: Chem3D Basics 5 Getting around 5 User interface preferences 9 Background settings 10 Sample files 10 Saving to Dropbox 10 Chapter 3: Basic Model Building 12 Default settings 12 Selecting a display mode 12 Using bond tools 13 Using the ChemDraw panel 15 Using other 2D drawing packages 15 Building from text 16 Adding fragments 18 Selecting atoms and bonds 18 Atom charges 21 Object position 23 Substructures 24 Refining models 27 Copying and printing 29 Finding structures online 32 Chapter 4: Displaying Models 35 © Copyright 1998-2017 PerkinElmer Informatics Inc., All rights reserved. ii Chem3D 17.0 Display modes 35 Atom and bond size 37 Displaying dot surfaces 38 Serial numbers 38 Displaying atoms 39 Atom symbols 40 Rotating models 41 Atom and bond properties 44 Showing hydrogen bonds 45 Hydrogens and lone pairs 46 Translating models 47 Scaling models 47 Aligning models 47 Applying color 49 Model Explorer 52 Measuring molecules 59 Comparing models by overlay 62 Molecular surfaces 63 Using stereo pairs 72 Stereo enhancement 72 Setting view focus 73 Chapter 5: Building Advanced Models 74 Dummy bonds and dummy atoms 74 Substructures 75 Bonding by proximity 78 Setting measurements 78 Atom and building types 81 Stereochemistry 85 © Copyright 1998-2017 PerkinElmer Informatics Inc., All rights reserved. iii Chem3D 17.0 Building with Cartesian