Efficient Quantum Chemical Calculation of Structure Ensembles and Free Energies for Nonrigid Molecules.
Stefan GrimmeFabian BohleAndreas HansenPhilipp PrachtSebastian SpicherMarcel StahnPublished in: The journal of physical chemistry. A (2021)
The application of quantum chemical, automatic multilevel modeling workflows for the determination of thermodynamic (e.g., conformation equilibria, partition coefficients, pKa values) and spectroscopic properties of relatively large, nonrigid molecules in solution is described. Key points are the computation of rather complete structure (conformer) ensembles with extremely fast but still reasonable GFN2-xTB or GFN-FF semiempirical methods in the CREST searching approach and subsequent refinement at a recently developed, accurate r2SCAN-3c DFT composite level. Solvation effects are included in all steps by accurate continuum solvation models (ALPB, (D)COSMO-RS). Consistent inclusion of thermostatistical contributions in the framework of the modified rigid-rotor-harmonic-oscillator approximation (mRRHO) based on xTB/FF computed PES is also recommended.
Keyphrases
- molecular dynamics
- density functional theory
- molecular dynamics simulations
- molecular docking
- high resolution
- ionic liquid
- computed tomography
- monte carlo
- deep learning
- machine learning
- crystal structure
- magnetic resonance imaging
- solid phase extraction
- molecularly imprinted
- diffusion weighted imaging
- magnetic resonance