Modeling Human Serum Albumin Tertiary Structure to Teach Upper-Division Chemistry Students Bioinformatics and Homology Modeling Basics

Abstract

A homology modeling laboratory experiment has been developed for an introductory molecular modeling course for upper-division undergraduate chemistry students. With this experiment, students gain practical experience in homology model preparation and assessment as well as in protein visualization using the educational version of PyMOL state-of-the-art molecular graphics. Students create a human serum albumin homology model with relatively high resolution at 1.77 Å (heavy atom model) and with reasonable values for bond lengths, angles, and dihedrals. The suggested tasks integrate different fundamental aspects of structural biology and protein modeling. Ramachandran plots and side chain rotamers are discussed. The assignments are shown to be good not only to teach homology modeling basics, but also to introduce several other concepts of structural bioinformatics such as protein sequence data mining, basic local alignment search tool (BLAST), and multiple sequence alignment. Homology modeling is demonstrated to be a cornerstone in molecular docking and drug design projects if the crystal structure of the protein of interest is not yet determined.