(362a) Computational Studies of Mechanical Stresses On Proteins in the Glassy State

Authors: 
Hatch, H. W. - Presenter, Princeton University
Debenedetti, P. G. - Presenter, Princeton University


Proteins and other labile biochemicals are stabilized in carbohydrate-water solutions, which may be lyophilized into amorphous solids as a method for long-term storage. Despite the widespread use of carbohydrates to stabilize proteins, the mechanism of stabilization is not well understood. The goal of the computational studies described herein is to understand the mechanism of protein stabilization in the glassy state. As a result of experimental studies of annealing following lyophilization, it has been suggested that microscopic mechanical stresses play an important role in the stabilization of proteins. Probing microscopic mechanical stresses experimentally for biomolecules, however, remains a challenge. Simulation techniques, on the other hand, may be used to investigate microscopic mechanical stresses and their role in affecting protein stabilization by carbohydrates in the glassy state. A theoretical formalism has been developed and successfully implemented computationally; this approach allows calculation of atomic-level stresses on proteins in solution and in the glassy state. Results will be presented for two model proteins, ubiquitin and keratin. The influence of the quenching rate on stresses in the glassy state, as well as a rigorous analysis that identifies statistically significant stress concentrations, will be discussed. Two important goals of this work are to relate mechanical stresses to changes in secondary structure, and to build the basis for a bioinformatics capability relating to the behavior of proteins in glassy matrices of varying composition.