Method Development for Efficient Force Field Calibration and Solubility Studies in NHC-Au(I) Complexes

• Applicant: Professorin Dr.-Ing. Gabriele Raabe
• Subject Area: Technical Thermodynamics ; Physical Chemistry of Molecules, Liquids and Interfaces, Biophysical Chemistry
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 566872896

The subject of the proposed project is the development of molecular models and simulation methods to enable reliable logPow predictions and systematic molecular dynamics (MD) studies of relevant interactions of N-heterocyclic carbene (NHC) gold complexes as innovative anti-infectives and cancer therapeutics. The currently inadequate parameterization of metals in molecular models hinders the successful application of MD studies to organometallic complexes. Therefore, the parameterization of metals is a central component of this project, for which a sequential Bayesian calibration method will be developed and applied to the molecular models GAFF/IPolQ-Mod+LJ-Fit and GAFF2/RESP – aimed at determining transferable force field parameters for (NHC)Au’Cl and biscarbene [Au(NHC)2]+ complexes as an important subgroup of NHC-Au compounds. To enable efficient logPow predictions by the "alchemical method," a machine learning model will be developed to predict starting values for the distribution of the intermediate states. Based on the parametrized models, MD studies will be conducted to analyse the interactions of NHC-Au(I) complexes with the solvents water and octanol - as lipid cell membrane model - to identify influencing factors. Through the development of efficient simulation methods with a robust parameterization, this project aims to enhance the applicability of MD simulations in the rational drug design of (NHC)-Au complexes.

• DFG Programme: Research Grants