Title: COMPUTATIONAL GENERATION INHIBITOR-BOUND CONFORMERS OF P38 MAP KINASE AND COMPARISON WITH EXPERIMENTS
Abstract: Biocomputing 2011, pp. 181-192 (2010) Open AccessCOMPUTATIONAL GENERATION INHIBITOR-BOUND CONFORMERS OF P38 MAP KINASE AND COMPARISON WITH EXPERIMENTSAHMET BAKAN and IVET BAHARAHMET BAKANDepartment of Computational and Systems Biology, School of Medicine, University of Pittsburgh, 3501 Fifth Ave, Suite 3064 BST3, Pittsburgh, PA, USA and IVET BAHARDepartment of Computational and Systems Biology, School of Medicine, University of Pittsburgh, 3501 Fifth Ave, Suite 3064 BST3, Pittsburgh, PA, USAhttps://doi.org/10.1142/9789814335058_0020Cited by:4 (Source: Crossref) PreviousNext AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsRecommend to Library ShareShare onFacebookTwitterLinked InRedditEmail Abstract: The p38 MAP kinases play a critical role in regulating stress-activated pathways, and serve as molecular targets for controlling inflammatory diseases. Computer-aided efforts for developing p38 inhibitors have been hampered by the necessity to include the enzyme conformational flexibility in ligand docking simulations. A useful strategy in such complicated cases is to perform ensemble-docking provided that a representative set of conformers is available for the target protein either from computations or experiments. We explore here the abilities of two computational approaches, molecular dynamics (MD) simulations and anisotropic network model (ANM) normal mode analysis, for generating potential ligand-bound conformers starting from the apo state of p38, and benchmark them against the space of conformers (or the reference modes of structural changes) inferred from principal component analysis of 134 experimentally resolved p38 kinase structures. ANM-generated conformations are found to provide a significantly better coverage of the inhibitor-bound conformational space observed experimentally, compared to MD simulations performed in explicit water, suggesting that ANM-based sampling of conformations can be advantageously employed as input structural models in docking simulations. FiguresReferencesRelatedDetailsCited By 4Cited by lists all citing articles based on Crossref citation.Effect of Lithium Drug on Binding Affinities of Glycogen Synthase Kinase-3 β to Its Network Partners: A New Computational ApproachMaryam Rouhani and Hamid Hadi-Alijanvand17 September 2021 | Journal of Chemical Information and Modeling, Vol. 61, No. 10Allostery as Structure‐Encoded Collective DynamicsIndira H. Shrivastava, Chang Liu, Anindita Dutta, Ahmet Bakan and Ivet Bahar10 January 2020re-TAMD: exploring interactions between H3 peptide and YEATS domain using enhanced samplingGilles Lamothe and Thérèse E. Malliavin3 April 2018 | BMC Structural Biology, Vol. 18, No. 1Normal Mode-Based Approaches in Receptor Ensemble DockingClaudio N. Cavasotto24 November 2011 Recommended Biocomputing 2011Metrics History PDF download