Danni L. Harris, Ph.D.

2495 Old Middlefield Way
Mountain View, CA 94043-2316
(650) 210-0310  Ext. 105(voice) - (650) 210-0318 (fax)

Ph.D. Physical Chemistry, 1984, Purdue University


The figure to the left shows the electrostatic potential surface of the reduced oxyferrous heme species and an associated hydrogen bond network computed in  B3LYP DFT calculations and mapped on the Connolly surface. The initial coordinates for the model system used in the DFT calculations were taken from MD trajectories for the P450eryF system modeled in the  reduced oxyferrous heme species form. The electrostatic potential surface reveals that the significant charge density on the bound dioxygen leads to significant nonbonded interactions with the associated water network. The characteristics of this species therefore leads naturally to robust hydrogen bond networks with short, strong hydrogen bonds. Such hydrogen bonding features lead naturally to low barrier proton transfer to the distal oxygen of the reduced oxyferrous heme and facilitates compound I formation.

5-point pharmacophore for ligands recognizing GABA(A) receptor subtypes containing the alpha-1 subunit which have shown in mutational studies in mice to be associated with sedative effects. The pharmacophore was determined from conformational libraries and quantum chemical calculations using an in house program MOLMOD. The present pharmacophore leads to quantitative binding (3D-QSAR) models for this endpoint. Multivariate discriminant analysis based on bioactive conformations indicate several sterochemical variables are linked with activation at this endpoint.