Computational study to construct mimics of helical domains in proteins

CHED 1380

Megan E. Messick, memessick09@transy.edu, Courtney K. Wilson, cowilson@transy.edu, Elizabeth A. Woods, eawoods09@transy.edu, Eva Csuhai, ecsuhai@transy.edu, and Alan C. Goren, agoren@transy.edu. Division of Natural Sciences and Mathematics, Transylvania University, 300 North Broadway, Lexington, KY 40408
Terphenyls and similar structures have been proposed as analogs of helical domains in proteins. Side-chains that provide conformational restrictions result in a 3-D structure simulating helical dimensions. Computational chemistry may provide insight and potential starting points for future construction of target structures. The terphenyl scaffold provides twelve sites for attaching side-chains differing in size and polarity. Terphenyl side-chain positioning mimics amino acids arrangement in alpha-helices of proteins. In collaboration with biochemists, we have computed the energies and torsional characteristics of terphenyls with a variety of organic functional groups. All calculations were performed using density functional theory with exchange-correlation functional (B3LYP) and 6-31G(d) basis sets. Vibrational frequencies were calculated for all optimized geometries. Solvent effects were calculated utilizing the Conductor-Like Polarizable Continuum Model (CPCM). The optimized structures appear to represent a balance between minimizing steric hindrance and maximizing pi-delocalization. Calculations reveal that the more bulky the side-chain, the larger the torsional angle between neighboring phenyl groups.