Abstract: This disclosure relates to an inhibitor of MELK and/or ROR2, preferably for use in the treatment of diffuse intrinsic pontine glioma (DIPG), wherein the DIPG is preferably characterized by overexpression of MELK and/or overexpression of ROR2. The inhibitor may be combined with a P-glycoprotein inhibitor, an Abcb1a inhibitor, Abcb1b inhibitor, mannitol, or an Abcg2 inhibitor.

Abstract: The invention generally relates to computational analysis and modeling of molecular structures and intermolecular interactions. More particularly, the invention concerns methods for determining the conformation of molecules including biomolecules, and methods for determining the molecular structure of complexes comprising such molecules. The invention may generally involve a reiterative communication between a docking and side-chain packing simulation on the one hand and a molecular dynamics (MD) simulation on the other hand. This allows to analyze backbone conformation changes that may arise due to intermolecular interactions upon the formation of a complex, yielding information more representative of the actual conformational events in and/or state of the complex. The invention may be used inter alia for analyzing and modeling the structure of proteins, protein-protein and protein-ligand interactions, and for protein and ligand design and engineering.

Abstract: A method for generating information of a 3-dimensional molecular structure of a molecule, said method being executable by a computer under the control of a program stored in the computer, said method comprising the steps of: (a) receiving a 3-dimensional representation of the molecular structure of said molecule, comprising a first set of residue portions and a template; (b) repeating an optimization cycle, wherein a set of (b1) modifying the molecular structure of one or more of the first set of residue portions, (b2) relaxing said modified structure, and (b3) calculating an energy value of the structure and comparing said calculated value with a prestored base value or with a value calculated in a previously performed step (b3), is repeated; (c) until a predetermined criterion is fulfilled; and (d) outputting a data structure comprising information extracted from any of these steps to a storage medium or to a consecutive method.