title: Parameterization of aromatic azido groups: application as photoaffinity probes in molecular dynamics studies.
abstract: The accuracy of molecular dynamics (MD) simulations is limited by the availability of parameters for the molecular system of interest. In most force fields, parameters of common chemical groups are already present. With the development of novel small organic molecules as probes to study biological systems, more chemical groups require parameterization. An azide group is often used in studies of biological systems but computational studies are still impeded by the lack of parameters. In this paper, we present a set of molecular mechanics (MM) parameters for aromatic and aliphatic azido groups, and their application in MD simulations of a photoaffinity probe currently used in our laboratory for mapping binding modes available in the active site of histone deacetylases. The parameters were developed for the generalized Amber force field (GAFF) using density functional theory (DFT) calculations at B3LYP 6-311G(d) level. The parameters were validated by geometry optimization and MD simulations.
authors.affiliation: Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Gilles
authors.initials: G
authors.lastname: Pieffet
authors.forename: Pavel A
authors.initials: PA
authors.lastname: Petukhov
mesh_terms: D001386:Azides / Q000737:chemistry*; D003198:Computer Simulation; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D015335:Molecular Probes / Q000737:chemistry*; D019920:Photoaffinity Labels / Q000737:chemistry*; D012399:Rotation; D013499:Surface Properties
chemical_list: D001386:Azides; D015335:Molecular Probes; D019920:Photoaffinity Labels