Abstract: The present invention relates to identification of a compound which inhibits the enzyme NMPRTase and glioma cancer cell growth and further used for glioma therapy. Pre-B-cell colony enhancing factor 1 gene (PBEF1) encodes nicotinamide phosphoribosyltransferase (NMPRTase), which catalyzes the rate limiting step in the salvage pathway of NAD metabolism in mammalian cells. PBEF1 transcript and protein levels have been shown to be elevated in glioblastoma and a chemical inhibitor of NMPRTase has been shown to specifically inhibit cancer cells. Here a structure based drug discovery approach has been reported with an aim to develop novel inhibitors for glioblastoma therapy. Present invention relates to virtual screening using docking of ligands from a large library of 13,000 compounds against NMPRTase as the macromolecular target resulting in short listing of 34 possible ligands, of which six were tested experimentally, using the NMPRTase enzyme inhibition assay and further with the glioma cell viability assays.

Abstract: The present invention relates to identification of a compound which inhibits the enzyme NMPRTase and glioma cancer cell growth and further used for glioma therapy. Pre-B-cell colony enhancing factor 1 gene (PBEF1) encodes nicotinamide phosphoribosyltransferase (NMPRTase), which catalyses the rate limiting step in the salvage pathway of NAD metabolism in mammalian cells. PBEF1 transcript and protein levels have been shown to be elevated in glioblastoma and a chemical inhibitor of NMPRTase has been shown to specifically inhibit cancer cells. Here a structure based drug discovery approach has been reported with an aim to develop novel inhibitors for glioblastoma therapy. Present invention relates to virtual screening using docking of ligands from a large library of 13,000 compounds against NMPRTase as the macromolecular target resulting in short listing of 34 possible ligands, of which six were tested experimentally, using the NMPRTase enzyme inhibition assay and further with the glioma cell viability assays.

Abstract: Using annotated structural descriptions and binding data for two, four or more input ligand molecules known to bind to a given protein target, a profile of the ligand molecules can be created by identifying patches of ligand molecules which have similar chemical and/or stereochemical descriptions, scored with the use of a weight dataset (e.g., substitution matrix). A database containing annotated molecular descriptions can be searched according to the profile to identify, for example, additional ligands that can bind to the protein target. Information such as the input ligands, the additional ligands, and literature related to these molecules, and modeling tools can be displayed in a user interface.

Abstract: A one-dimensional structural description of a ligand molecule can be annotated to include, for one or more atoms, information from a force field database. The information can be provided by an Assisted Model Building and Energy Refinement parameter list or a similar source. The annotation can be carried out using one or more intermediate structural description formats and can include identifying one or more fragment types that make up the ligand molecule.

Abstract: Using annotated structural descriptions and binding data for two, four or more input ligand molecules known to bind to a given protein target, a profile of the ligand molecules can be created by identifying patches of ligand molecules which have similar chemical and/or stereochemical descriptions, scored with the use of a weight dataset (e.g., substitution matrix). A database containing annotated molecular descriptions can be searched according to the profile to identify, for example, additional ligands that can bind to the protein target. Information such as the input ligands, the additional ligands, and literature related to these molecules, and modeling tools can be displayed in a user interface.

Abstract: A one-dimensional structural description of a ligand molecule can be annotated to include, for one or more atoms, information from a force field database. The information can be provided by an Assisted Model Building and Energy Refinement parameter list or a similar source. The annotation can be carried out using one or more intermediate structural description formats and can include identifying one or more fragment types that make up the ligand molecule.