Effiziente und Genaue Simulationsmethoden zur Berechnung von freien Energien, Enthalpien und Entropien
Abstract
Computational, structure-based, drug design offers insight at an atomic resolution, which is commonly not attainable by experimental means. Detailed calculations on protein-ligand interactions help to rationalize and predict experimental findings. An accurate, yet efficient, calculation of binding free energies is essential in this respect. In addition, knowledge concerning the enthalpic and entropic contributions are highly relevant to determine novel drug design strategies and to understand the underlying principles of ligand binding. Currently available methods to address ligand affinity either do not include all relevant contributions to the binding free energy, or are too computationally demanding to be applied straightforwardly. In addition, calculations on enthalpy and entropy for drug design purposes are very rare, due to the difficulty in calculating these accurately. This proposal describes the research that leads the way to new, standard applications to be used in drug design processes in academia and industry. Furthermore, we propose to investigate the enthalpic and entropic contributions to ligand binding by utilising the enthalpy-entropy compensation known from solvation experiments. This leads to the definition of a ligand-surroundings enthalpy and entropy, which conveys more information than the experimentally accessible enthalpy and entropy of ligand binding.
Statistische Thermodynamik Moleculardynamiksimulationen Enhanced sampling methoden
Publikationen
Mitarbeiter*innen
Chris Oostenbrink
Univ.Prof. Dr. Chris Oostenbrink
chris.oostenbrink@boku.ac.at
Tel: +43 1 47654-89401, 89411, 89419
Projektleiter*in
01.01.2011 - 31.12.2015