Lyophilization can induce aggregation in therapeutic proteins, but the relative importance of protein structure, formulation and processing conditions are poorly understood. To evaluate the contribution of protein structure to lyophilization-induced aggregation, fifteen proteins were co-lyophilized with each of five excipients. Extent of aggregation following lyophilization, measured using size-exclusion chromatography, was correlated with computational and biophysical protein structural descriptors via multiple linear regression. Descriptor selection was performed using exhaustive search and forward selection. The results demonstrate that, for a given excipient, extent of aggregation is highly correlated by eight to twelve structural descriptors. Leave-one-out cross validation showed that the correlations were able to successfully predict the aggregation for a protein "left out" of the data set. Selected descriptors varied with excipient, indicating both protein structure and excipient type contribute to lyophilization-induced aggregation. The results show some descriptors used to predict protein aggregation in solution are useful in predicting lyophilized protein aggregation. (c) 2013 Elsevier Ltd. All rights reserved.