Normal-Mode Analysis of the Glycine Alpha1 Receptor by Three Separate Methods

Predicting collective dynamics and structural changes in biological macromolecules is pivotal toward a
better understanding of many biological processes. Limitations due to large system sizes and inaccessible
time scales have prompted the development of alternative techniques for the calculation of such motions. In
this work, we present the results of a normal-mode analysis technique based on molecular mechanics that
enables the calculation of accurate force-field based vibrations of extremely large molecules and compare
it with two elastic network approximate models. When applied to the glycine alpha1 receptor, all three
normal-mode analysis algorithms demonstrate an “iris-like” gating motion. Such gating motions have
implications for understanding the effects of anesthetic and other ligand binding sites and for the means of
transducing agonist binding into ion channel opening. Unlike the more approximate methods, molecular
mechanics based analyses can also reveal approximate vibrational frequencies. Such analyses may someday
allow the use of protein dynamics elucidated via normal-mode calculations as additional endpoints for future
drug design.