Biomedical subjects

Michael E Beck

Publications and source records attributed to Michael E Beck.

3 recordsLinked to original sources

PubMed2003

Implementation of a general multireference configuration interaction procedure with analytic gradients in a semiempirical context using the graphical unitary group approach.

The graphical unitary group approach has been applied in an efficient implementation of a general multireference configuration interaction (MRCI) method for use with small active molecular orbital spaces in a semiempirical framework. Gradients can be computed analytically for molecular orbitals from a closed-shell or a half-electron open-shell Hartree-Fock calculation. CPU times for single point energy and gradient calculations are reported. The code allows MRCI geometry optimizations of large molecules, as illustrated for the singlet ground state and the four lowest triplet states of fullerene C(76).

Journal Article↗

PubMed2002

Prediction of aqueous solubility of drugs and pesticides with COSMO-RS.

The COSMO-RS method, originally developed for the prediction of liquid-liquid and liquid-vapor equilibrium constants based on quantum chemical calculations, has been extended to solid compounds by addition of a heuristic expression for the Gibbs free energy of fusion. By this addition, COSMO-RS is now capable of a priori prediction of aqueous solubilities of a wide range of typical neutral drug and pesticide compounds. Only three parameters in the heuristic expression have been fitted on a data set of 150 drug-like compounds. On these data an rms deviation of 0.66 log-units was achieved. Later, the model was tested on a set of 107 pesticides, which have been critically selected based on two experimental data sources and by a crosscheck with an independent HQSAR model. On this data set an rms of 0.61 log-units was achieved, without any adjustments to the structurally extremely diverse pesticides. This result verifies the ability of this extended COSMO-RS to predict aqueous solubilities of drugs and pesticides of almost arbitrary structural classes. The new method is COSMO-RSol.

Artificial Intelligence↗

PubMedDate not supplied

Do Fukui function maxima relate to sites of metabolism? A critical case study.

The usefulness of local reactivity descriptors for understanding drug metabolism is investigated. Electrophilic Fukui functions are calculated for 18 drugs and 11 agrochemicals and their relation to experimentally observed metabolites is discussed. Maxima of the Fukui functions correspond to major sites of metabolic attack in many examples, facilitating a posteriori understanding of experimental findings. In the second part of the paper, the nature of the electrophilic oxidant species in cytochromes, called "Compound I" (Cpd I), is investigated within the Fukui framework. Nucleophilic Fukui functions are calculated involving the relevant spin states of Cpd I, allowing a more qualitative, intuitive understanding of its reactivity.

Agrochemicals↗