Small molecule-protein interactions involving Substrate 4 of the Vitamin D receptor using computational alanine scanning
Grant, Deion; Madura, Jeffry D.
Department of Chemistry and Biochemistry
Center for Computational Sciences
Duquesne University, Pittsburgh, PA 15281
Vitamin D is an essential enzyme that assists in the mineralization of bone, bone growth and bone remodeling. Experiments have been done to investigate the allosteric effects of ligands in the function of nuclear receptors using a method known as alanine scanning. Alanine scanning involves the mutation of binding pocket amino acids to alanine so that the importance of that amino acid in the binding pocket is determined. The free energy perturbation method in conjunction with the thermodynamic cycle is used to perform computational alanine screening. Using Substrate 4 in the vitamin D receptor the computational alanine scanning method can be validated. Preliminary results of the computational alanine scanning method will be presented in the poster.