Conformational Ensembles from Experimental Data and Computer Simulations

Conformational Ensembles from Experimental Data

and Computer Simulations

Poster Abstracts

27-POS

Board 27

Assessment of Peptide Conformational Landscape and Dynamics by Amide I' Infrared

Spectroscopy and MD Simulations

Chi-Jui Feng

, Andrei Tokmakoff.

University of Chicago, Chicago, IL, USA.

Amide I’ spectroscopy has growing capabilities for probing complex protein structures including

intrinsically disordered regions. With amide I' spectroscopic maps, one can structurally interpret

experimental spectra from MD trajectories, providing a route to disordered protein ensemble

refinement. However, few studies have quantitatively evaluated the quality of these

spectroscopic simulations and their ability to interpret protein conformational distributions and

dynamics. Such studies will help understand how much structural and dynamical information can

be obtained from these methods.

As a proof of principle study, we compared experimental and simulated IR and 2D IR spectra of

Ala-Ala and Ala-Ala-Ala. In Ala-Ala, the correlation time of the amide I’ frequency-frequency

correlation function (FFCF) is related to the fluctuating hydrogen bonding environments to the

amide group. 2D IR spectra of Ala-Ala-Ala provide information on the average angle between

the two amide carbonyl groups, giving constraints on underlying conformational distributions.

Comparing experimental spectra with spectra simulated from several force fields, we are able to

characterize the conformational distribution of trialanine and also assess the predictions of these

force fields. We show that its structure is dominated by ppII conformer, with minor population of

β conformer.

These analytical tools are being developed to interpret more complicated protein spectra in

combination with site-specific isotope labeling. We use human insulin as an illustration to

understand the structural changes during the monomer-dimer transition, with the focus on the

dissociation of the inter-chain β-sheet, and the hinging motion and disorder of the monomer B-

chain.