Glucagon Modeled as a Coarse - Grained Bead - String Polymer

Joon Bok Lee 06/15/2012 CHE 210D – Spring 2012 Glucagon Modeled as a Coarse-Grained Bead-String Polymer Final Project Summary Glucagon and insulin play major roles in regulating blood glucose levels, and people with type 1 diabetes mellitus need exogenous sources of these hormones for survival. One major issue faced by glucagon pumps that automate these exogenous injections is the problem of stability, as glucagon rapidly forms precipitates upon standard clinical preparation which greatly decrease their shelf lives. To understand general trends that cause these effects and determine conditions under which glucagon can be stored in an aqueous solution, a molecular dynamics simulation was conducted to illustrate the properties of a glucagon molecule under varying pH and temperature conditions. Glucagon was modeled as a bead-string polymer of 29 coarse-grain units, with each unit representing a separate amino acid and thus having its individual parameters, including different radii and charge. The changes in pH was modeled as changes in the total charge of each amino acid unit based on the charge of its R-group(s), and an Anderson thermostat was utilized to model changes in temperature. The radius of gyration of the simulated glucagon molecule increases with the distance from neutral pH. A similar, but plateauing trend can be seen with increasing simulation temperature. These trends have comparable counterparts to experimental results found in literature.