title: Computational exploration of a protein receptor binding space with student proposed peptide ligands.
abstract: Computational molecular docking is a fast and effective in silico method for the analysis of binding between a protein receptor model and a ligand. The visualization and manipulation of protein to ligand binding in three-dimensional space represents a powerful tool in the biochemistry curriculum to enhance student learning. The DockoMatic tutorial described herein provides a framework by which instructors can guide students through a drug screening exercise. Using receptor models derived from readily available protein crystal structures, docking programs have the ability to predict ligand binding properties, such as preferential binding orientations and binding affinities. The use of computational studies can significantly enhance complimentary wet chemical experimentation by providing insight into the important molecular interactions within the system of interest, as well as guide the design of new candidate ligands based on observed binding motifs and energetics. In this laboratory tutorial, the graphical user interface, DockoMatic, facilitates docking job submissions to the docking engine, AutoDock 4.2. The purpose of this exercise is to successfully dock a 17-amino acid peptide, α-conotoxin TxIA, to the acetylcholine binding protein from Aplysia californica-AChBP to determine the most stable binding configuration. Each student will then propose two specific amino acid substitutions of α-conotoxin TxIA to enhance peptide binding affinity, create the mutant in DockoMatic, and perform docking calculations to compare their results with the class. Students will also compare intermolecular forces, binding energy, and geometric orientation of their prepared analog to their initial α-conotoxin TxIA docking results.
authors.affiliation: Department of Chemistry and Biochemistry, Boise State University, Boise, Idaho, 83725.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: King
authors.affiliation: Department of Chemistry and Biochemistry, Boise State University, Boise, Idaho, 83725.
authors.forename: Paul
authors.initials: P
authors.lastname: Phillips
authors.affiliation: Department of Chemistry and Biochemistry, Biomolecular Sciences PhD Program, Boise State University, Boise, Idaho, 83725.
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Turner
authors.affiliation: Department of Chemistry and Biochemistry, Boise State University, Boise, Idaho, 83725.
authors.forename: Michael
authors.initials: M
authors.lastname: Katz
authors.affiliation: Department of Chemistry and Biochemistry, Boise State University, Boise, Idaho, 83725.
authors.forename: Sarah
authors.initials: S
authors.lastname: Lew
authors.affiliation: Department of Computer Science and Engineering, Boise State University, Boise, Idaho, 83725.
authors.forename: Sarah
authors.initials: S
authors.lastname: Bradburn
authors.affiliation: Department of Computer Science and Engineering, Boise State University, Boise, Idaho, 83725.
authors.forename: Tim
authors.initials: T
authors.lastname: Andersen
authors.affiliation: Department of Chemistry and Biochemistry, Boise State University, Boise, Idaho, 83725.
authors.forename: Owen M
authors.initials: OM
authors.lastname: McDougal
mesh_terms: D001665:Binding Sites; D001671:Biochemistry / Q000193:education*; D019295:Computational Biology; D062105:Molecular Docking Simulation; D010455:Peptides / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D013334:Students
chemical_list: D010455:Peptides; D011956:Receptors, Cell Surface
keywords: computational chemistry; computers in research and teaching