MOLECULAR SIMULATIONS OF CHEMICAL STABILITY OF MODEL PEPTIDES IN AMORPHOUS POLYMERS

University Of Kentucky Research Foundation, Lexington KY

Investigators

Abstract

Due to the inherent instability of protein/peptide drugs in aqueous solution, the successful formulation of these compounds in lyophilized form has become an important activity within the pharmaceutical industry. However, the extent to which the stability of a given protein/peptide is improved in the amorphous solid-state depends on many variables including moisture, temperature, the viscoelastic properties of the solid, chemical nature of the excipients and impurities present, and the nature of the degradation pathways. Molecular dynamics simulations are uniquely suited to the exploration of various molecular details which are important in the degradation of proteins/peptides in amorphous solids. The researchers will investigate how changes in molecular mobility and conformational flexibility in amorphous matrices influence both the formation of reactive intermediates and the subsequent partitioning of these reactive intermediates to products, which depends on the relative translational and rotational mobility of either the protein itself or smaller molecules which may be participants in the overall reaction.