caa a22 4500 467938946 CHVBK 20180406153006.0 cr unu---uuuuu 170328e20060501xx s 000 0 eng 10.1007/s10822-006-9057-z doi (NATIONALLICENCE)springer-10.1007/s10822-006-9057-z Three dimensional model of severe acute respiratory syndrome coronavirus helicase ATPase catalytic domain and molecular design of severe acute respiratory syndrome coronavirus helicase inhibitors [Elektronische Daten] [Marcin Hoffmann, Krystian Eitner, Marcin von Grotthuss, Leszek Rychlewski, Ewa Banachowicz, Tomasz Grabarkiewicz, Tomasz Szkoda, Andrzej Kolinski] The modeling of the severe acute respiratory syndrome coronavirus helicase ATPase catalytic domain was performed using the protein structure prediction Meta Server and the 3D Jury method for model selection, which resulted in the identification of 1JPR, 1UAA and 1W36 PDB structures as suitable templates for creating a full atom 3D model. This model was further utilized to design small molecules that are expected to block an ATPase catalytic pocket thus inhibit the enzymatic activity. Binding sites for various functional groups were identified in a series of molecular dynamics calculation. Their positions in the catalytic pocket were used as constraints in the Cambridge structural database search for molecules having the pharmacophores that interacted most strongly with the enzyme in a desired position. The subsequent MD simulations followed by calculations of binding energies of the designed molecules were compared to ATP identifying the most successful candidates, for likely inhibitors—molecules possessing two phosphonic acid moieties at distal ends of the molecule. Springer Science+Business Media B.V., 2006 SARS nationallicence Inhibitors nationallicence Drug design nationallicence Computational chemistry nationallicence Bioinformatics nationallicence Hoffmann Marcin BioInfoBank Institute, ul. Limanowskiego 24A, 60-744, Poznan, Poland aut Eitner Krystian BioInfoBank Institute, ul. Limanowskiego 24A, 60-744, Poznan, Poland aut von Grotthuss Marcin BioInfoBank Institute, ul. Limanowskiego 24A, 60-744, Poznan, Poland aut Rychlewski Leszek BioInfoBank Institute, ul. Limanowskiego 24A, 60-744, Poznan, Poland aut Banachowicz Ewa Bioinformatics Unit, Department of Physics, Adam Mickiewicz University, ul. Umultowska 85, 61-614, Poznan, Poland aut Grabarkiewicz Tomasz BioInfoBank Institute, ul. Limanowskiego 24A, 60-744, Poznan, Poland aut Szkoda Tomasz Respiratory Virus Laboratory, Department of Virology, National Institute of Hygiene, ul. Chocimska 24, 00-791, Warsaw, Poland aut Kolinski Andrzej Faculty of Chemistry, Warsaw University, ul. Pasteura 1, 02-093, Warsaw, Poland aut Journal of Computer-Aided Molecular Design Kluwer Academic Publishers 20/5(2006-05-01), 305-319 0920-654X 20:5<305 2006 20 10822 https://doi.org/10.1007/s10822-006-9057-z text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10822-006-9057-z text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Hoffmann Marcin BioInfoBank Institute, ul. Limanowskiego 24A, 60-744, Poznan, Poland aut NATIONALLICENCE 700 1- Eitner Krystian BioInfoBank Institute, ul. Limanowskiego 24A, 60-744, Poznan, Poland aut NATIONALLICENCE 700 1- von Grotthuss Marcin BioInfoBank Institute, ul. Limanowskiego 24A, 60-744, Poznan, Poland aut NATIONALLICENCE 700 1- Rychlewski Leszek BioInfoBank Institute, ul. Limanowskiego 24A, 60-744, Poznan, Poland aut NATIONALLICENCE 700 1- Banachowicz Ewa Bioinformatics Unit, Department of Physics, Adam Mickiewicz University, ul. Umultowska 85, 61-614, Poznan, Poland aut NATIONALLICENCE 700 1- Grabarkiewicz Tomasz BioInfoBank Institute, ul. Limanowskiego 24A, 60-744, Poznan, Poland aut NATIONALLICENCE 700 1- Szkoda Tomasz Respiratory Virus Laboratory, Department of Virology, National Institute of Hygiene, ul. Chocimska 24, 00-791, Warsaw, Poland aut NATIONALLICENCE 700 1- Kolinski Andrzej Faculty of Chemistry, Warsaw University, ul. Pasteura 1, 02-093, Warsaw, Poland aut NATIONALLICENCE 773 0- Journal of Computer-Aided Molecular Design Kluwer Academic Publishers 20/5(2006-05-01), 305-319 0920-654X 20:5<305 2006 20 10822 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer