caa a22 4500 467938849 CHVBK 20180406153006.0 cr unu---uuuuu 170328e20060301xx s 000 0 eng 10.1007/s10822-006-9041-7 doi (NATIONALLICENCE)springer-10.1007/s10822-006-9041-7 Protein Alpha Shape (PAS) Dock: A new gaussian-based score function suitable for docking in homology modelled protein structures [Elektronische Daten] [Kristin Tøndel, Endre Anderssen, Finn Drabløs] Protein Alpha Shape (PAS) Dock is a new empirical score function suitable for virtual library screening using homology modelled protein structures. Here, the score function is used in combination with the geometry search method Tabu search. A description of the protein binding site is generated using gaussian property fields like in Protein Alpha Shape Similarity Analysis (PASSA). Gaussian property fields are also used to describe the ligand properties. The overlap between the receptor and ligand hydrophilicity and lipophilicity fields is maximised, while minimising steric clashes. Gaussian functions introduce a smoothing of the property fields. This makes the score function robust against small structural variations, and therefore suitable for use with homology models. This also makes it less critical to include protein flexibility in the docking calculations. We use a fast and simplified version of the score function in the geometry search, while a more detailed version is used for the final prediction of the binding free energies. This use of a two-level scoring makes PAS-Dock computationally efficient, and well suited for virtual screening. The PAS-Dock score function is trained on 218 X-ray structures of protein- ligand complexes with experimental binding affinities. The performance of PAS-Dock is compared to two other docking methods, AutoDock and MOE-Dock, with respect to both accuracy and computational efficiency. According to this study, PAS-Dock is more computationally efficient than both AutoDock and MOE-Dock, and gives a better prediction of the free energies of binding. PAS-Dock is also more robust against structural variations than AutoDock. Springer-Verlag 2006, 2006 Computational docking nationallicence Empirical score function nationallicence Gaussian property fields nationallicence Protein Alpha Shape Similarity Analysis (PASSA) nationallicence Virtual screening nationallicence Tøndel Kristin Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Laboratory Center, Erling Skjalgsons St. 1, N-7006, Trondheim, Norway aut Anderssen Endre Department of Chemistry, Norwegian University of Science and Technology, N-7491, Trondheim, Norway aut Drabløs Finn Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Laboratory Center, Erling Skjalgsons St. 1, N-7006, Trondheim, Norway aut Journal of Computer-Aided Molecular Design Kluwer Academic Publishers 20/3(2006-03-01), 131-144 0920-654X 20:3<131 2006 20 10822 https://doi.org/10.1007/s10822-006-9041-7 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10822-006-9041-7 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Tøndel Kristin Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Laboratory Center, Erling Skjalgsons St. 1, N-7006, Trondheim, Norway aut NATIONALLICENCE 700 1- Anderssen Endre Department of Chemistry, Norwegian University of Science and Technology, N-7491, Trondheim, Norway aut NATIONALLICENCE 700 1- Drabløs Finn Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Laboratory Center, Erling Skjalgsons St. 1, N-7006, Trondheim, Norway aut NATIONALLICENCE 773 0- Journal of Computer-Aided Molecular Design Kluwer Academic Publishers 20/3(2006-03-01), 131-144 0920-654X 20:3<131 2006 20 10822 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer