ProBiS-CHARMMing: Web Interface for Prediction and Optimization of Ligands in Protein Binding Sites.
Proteins often exist only as apo structures (unligated) in the Protein Data Bank, with their corresponding holo structures (with ligands) unavailable. However, apoproteins may not represent the amino-acid residue arrangement upon ligand binding well, which is especially problematic for molecular docking. We developed the ProBiS-CHARMMing web interface by connecting the ProBiS ( http://probis.cmm.ki.si ) and CHARMMing ( http://www.charmming.org ) web servers into one functional unit that enables prediction of protein-ligand complexes and allows for their geometry optimization and interaction energy calculation. The ProBiS web server predicts ligands (small compounds, proteins, nucleic acids, and single-atom ligands) that may bind to a query protein. This is achieved by comparing its surface structure against a nonredundant database of protein structures and finding those that have binding sites similar to that of the query protein. Existing ligands found in the similar binding sites are then transposed to the query according to predictions from ProBiS. The CHARMMing web server enables, among other things, minimization and potential energy calculation for a wide variety of biomolecular systems, and it is used here to optimize the geometry of the predicted protein-ligand complex structures using the CHARMM force field and to calculate their interaction energies with the corresponding query proteins. We show how ProBiS-CHARMMing can be used to predict ligands and their poses for a particular binding site, and minimize the predicted protein-ligand complexes to obtain representations of holoproteins. The ProBiS-CHARMMing web interface is freely available for academic users at http://probis.nih.gov.
Laboratory for Molecular Modeling, National Institute of Chemistry , Hajdrihova 19, SI-1000, Ljubljana, Slovenia.|Faculty of Mathematics, Natural Sciences and Information Technologies, University of Primorska , Glagoljaška 8, SI-6000, Koper, Slovenia.
Janez
J
Konc
Laboratory of Computational Biology, Biochemistry and Biophysics Center, National Heart, Lung and Blood Institute, National Institutes of Health , Bethesda, Maryland 20892, United States.
Benjamin T
BT
Miller
Faculty of Mathematics, Natural Sciences and Information Technologies, University of Primorska , Glagoljaška 8, SI-6000, Koper, Slovenia.
Tanja
T
Štular
Laboratory for Molecular Modeling, National Institute of Chemistry , Hajdrihova 19, SI-1000, Ljubljana, Slovenia.
Samo
S
Lešnik
Department of Chemistry, University of South Florida , 4202 East Fowler Ave., Tampa, Florida 33620, United States.
H Lee
HL
Woodcock
Laboratory of Computational Biology, Biochemistry and Biophysics Center, National Heart, Lung and Blood Institute, National Institutes of Health , Bethesda, Maryland 20892, United States.
Bernard R
BR
Brooks
Faculty of Mathematics, Natural Sciences and Information Technologies, University of Primorska , Glagoljaška 8, SI-6000, Koper, Slovenia.
Dušanka
D
Janežič
D001665:Binding Sites; D030562:Databases, Protein; D020407:Internet; D008024:Ligands; D008954:Models, Biological; D062105:Molecular Docking Simulation; D011485:Protein Binding; D011487:Protein Conformation; D060066:Protein Interaction Maps; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology; D012984:Software; D013816:Thermodynamics
D008024:Ligands; D011506:Proteins; D054852:Small Molecule Libraries