Solutions White Papers
Download DocumentQSAR Modeling of Drug Binding to Protein
β-Lactam Serum Binding and Albumin Binding AffinityLemont B. Kier
Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298
and
Lowell H. Hall, and L. Mark Hall
Department of Chemistry, Eastern Nazarene College, Quincy, MA 02170
Abstract
The binding of drugs and drug-like compounds to human serum albumin was modeled with topological descriptors of molecular structure. The MDL® QSAR software was used for the actual modeling and database management. Two types of experimental data were modeled: 1) percent bound drug (PAB) for 87 penicillins and also for 115 β-lactams, and 2) chromatographic retention index, logk(HSA), on immobilized albumin for 94 drugs. In both cases the electrotopological state indices (E-State) along with the molecular connectivity chi indices were found to be the basis of satisfactory models. The features of MDL QSAR were very useful in creating combination descriptors for several of the structure features that are important for albumin binding as well as developing the final models, managing database information and producing reports, tables and plots.
The β-lactam class of antibiotics. The common scaffolds of penicillins and cephalosporins with substitution points labeled R1, R2, and R3.
To read the complete white paper, click the Download Document link near the top of the this article.
