Biomedical subjects

S P van Helden

Publications and source records attributed to S P van Helden.

3 recordsLinked to original sources

PubMed1992

The conformational behaviour of complexes of alpha-cyclodextrin with p-chlorophenol and p-hydroxybenzoic acid in water as studied by molecular dynamics simulations.

Molecular dynamics simulations were performed to obtain information about the conformational behaviour and stabilization of alpha-cyclodextrin (alpha CD) complexes in water. Simulations of p-chlorophenol and p-hydroxybenzoic acid in alpha CD showed that the complex is a very flexible system. The guest compound rotates inside the cavity and partly moves in and out. alpha CD continuously adapts its conformation to the orientation of the guest compound (or vice versa): the hexagon of the glycosidic oxygen atoms is stretched parallel to the plane of the aromatic ring of the guest compound during 80% of the simulation. This suggests that Van der Waals interactions play an important role in the stabilization of the complex. Each intramolecular hydrogen bond between neighbouring glucose units is formed during 30-80% of the simulation. Hydrogen bonds between alpha CD and the guest compound, on the other hand, are rarely formed. Thus, intermolecular hydrogen bonding seems to play a minor role in the stabilization of alpha CD complexes.

Chlorophenols↗

PubMed1991

Modeling and conformation analysis of beta-cyclodextrin complexes.

A series of beta-cyclodextrin complexes containing various guest molecules was studied using computer-aided molecular modeling and conformation analysis techniques. The geometry of each complex was studied using crystallographic data. The positions of the glycosidic O4 atoms indicate that the beta-cyclodextrin molecules are elliptically distorted. This distortion can be related to the van der Waals volume of the guest molecules. This correlation is different for aromatic and non-aromatic guest compounds. Rigid body docking experiments demonstrated that in crystal structures the guest molecule occupies a position in the cavity of nearly minimum interaction energy when there are no other molecules having interactions with the guest molecule. From the crystallographic data several rules could be deduced which seem to determine the conformation of beta-cyclodextrin molecules in complexes. A procedure was developed to construct beta-cyclodextrin molecules that are able to encompass guest molecules having a given van der Waals volume.

Carbohydrate Conformation↗

PubMedDate not supplied

Quantitative structure-activity relationship studies of progesterone receptor binding steroids.

The selection of appropriate descriptors is an important step in the successful formulation of quantitative structure-activity relationships (QSARs). This paper compares a number of feature selection routines and mapping methods that are in current use. They include forward stepping regression (FSR), genetic function approximation (GFA), generalized simulated annealing (GSA), and genetic neural network (GNN). On the basis of a data set of steroids of known in vitro binding affinity to the progsterone receptor, a number of QSAR models are constructed. A comparison of the predictive qualities for both training and test compounds demonstrates that the GNN protocol achieves the best results among the 2D QSAR that are considered. Analysis of the choice of descriptors by the GNN method shows that the results are consistent with established SARs on this series of compounds.

Neural Networks, Computer↗