(188cr) A Molecular Dynamics Study of Carbohydrate Preferential Interactions with Small Proteins

Carbohydrates are extensively used as formulation excipients to reduce the aggregation of high-concentration formulations. Carbohydrates tend to be preferentially excluded from protein surfaces, thus stabilizing the monomer conformation. However, the exact molecular-level interactions that lead to protein stabilization are less well understood, but can be studied through the use of molecular dynamics simulations.

Here, we have used all-atom molecular dynamics simulations to model the behavior of α-Chymotrypsinogen A, bovine serum albumin, lysozyme, and ribonuclease A with carbohydrates including glycerol, sorbitol, glucose, sucrose, and trehalose. In agreement with experiment, the simulations indicate that all the carbohydrates are excluded from the protein surface.

In this work we will describe the relative strength of exclusion of the carbohydrates from the proteins as a whole as well as from particular patches on the protein surfaces, comparing behavior of different carbohydrates and interactions with different proteins. We will also examine the specific interactions of carbohydrate molecules with individual residues on the protein surfaces, including discussion of the role of hydrogen bonding in carbohydrate-protein interactions and of the interactions with hydrophobic and hydrophilic surface patches.