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.

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