Systematic enhancement of protein crystallization efficiency by bulk lysine-to-arginine (KR) substitution.

Structural genomics consortia established that protein crystallization is the primary obstacle to structure determination using x-ray crystallography. We previously demonstrated that crystallization propensity is systematically related to primary sequence, and we subsequently performed computational analyses showing that arginine is the most overrepresented amino acid in crystal-packing interfaces in the Protein Data Bank. Given the similar physicochemical characteristics of arginine and lysine, we hypothesized that multiple lysine-to-arginine (KR) substitutions should improve crystallization.

Parameterization of the miniPEG-Modified γPNA Backbone: Toward Induced γPNA Duplex Dissociation.

γ-Modified peptide nucleic acids (γPNAs) serve as potential therapeutic agents against genetic diseases. Miniature poly(ethylene glycol) (miniPEG) has been reported to increase solubility and binding affinity toward genetic targets, yet details of γPNA structure and dynamics are not understood. Within our work, we parameterized missing torsional and electrostatic terms for the miniPEG substituent on the γ-carbon atom of the γPNA backbone in the CHARMM force field.