Biophysical Society Thematic Meeting | Hamburg 2022

Biophysics at the Dawn of Exascale Computers

Poster Abstracts

30-POS Board 30 EQUILIBRIUM AND DYNAMIC PROPERTIES OF UNFOLDED POLYPEPTIDE CHAINS: A MARKOV CHAIN ANALYSIS OF INTERNAL POLYMER DYNAMICS Vipul Kumar 1 ; Thomas Kiefhaber 1 ; 1 Martin Luther University, Institute of Biochemistry and Biotechnology, Halle, Germany Contact formation between different segments of a polypeptide chain is the most elementary step of protein folding. However, carrying out experiments to study such rapid event has remained a challenge. We have been able to gain information on the dynamic and structural properties of unfolded polypeptide chains by using intrinsically disordered polypeptide sequences labeled with chromophore dyes at the two ends, to probe for the intrachain distance measurement and the intrachain diffusion coefficient by FRET 1 as well as to measure the rate constant of loop formation by triplet-triplet energy transfer 2 . These studies indicate a higher mobility of the residues close to the ends of the disordered chain as compared to the ones in the interior. To gain information on the origin of the experimentally observed higher mobility at the chain ends we explore the dynamics of unfolded polypeptide chains by Monte-Carlo simulations, where randomly selected sigma bonds are rotated arbitrarily within sterically allowed regime, followed by a Markov Chain analysis of the end-to-end distance transitions. The simulations, although not exact replica of physiological conditions, mimic the properties of a good solvent. This method, in combination with our previous experimental studies, provides the frequency of chain fluctuations, the flux of the ends to approach or recede from each other and the distance distributions. Finally, we discuss the unique properties of the ends of a chain and why loop formation between internal residues is slower than loop formation between the chain ends. References:1. Möglich A., Joder K., Kiefhaber T., (2006), PNAS 103, 12394- 123992. Fierz B., Kiefhaber T., (2006), JACS 129, 672-679

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