Toby G. Rossman, Ekaterina I. Goncharova, et al.
Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
An unambiguous understanding of the binding mode of human progesterone to its receptor still eludes experimental search. According to the X-ray structure of the ligand-binding domain, only one (O3) of the two keto groups at the ligand ends (O3 and O20) should play a role. This result is in conflict with chemical intuition and the results of site-directed mutagenesis experiments. Herein, we report classical molecular dynamics simulations that reveal the dynamic nature of the binding in solution, elucidate the reasons why X-ray studies failed to determine the role of O20, and clarify the effects of the mutations. The predictive power of the force field is ensured by the consistent introduction of a first-principles representation of the ligand.
Toby G. Rossman, Ekaterina I. Goncharova, et al.
Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Helgi I. Ingolfsson, Chris Neale, et al.
PNAS
E.W. Grundke, D. Henderson, et al.
Molecular Physics
Yan Chen, Joachim D. Müller, et al.
Methods: A Companion to Methods in Enzymology