Biophysical Society Thematic Meeting | Hamburg 2022

Biophysics at the Dawn of Exascale Computers

Poster Abstracts

8-POS Board 8 TOWARDS RATIONAL DESIGN OF BIOTECHNOLOGICAL ENZYMES: IS EXASCALE NEEDED FOR COMPUTATIONAL ANALYSIS OF NITRILE HYDRATASE IN NON-CLASSICAL SOLVENTS?

Julia A. Berdychowska 1,2 ; Wieslaw Nowak 1,2 ; Lukasz Peplowski 1,2 ; 1 Centre for Modern Interdisciplinary Technologies, Torun, Poland

2 Nicolaus Copernicus University in Torun, Department of Biophysics, Torun, Poland Green chemistry uses enzymes, and one of the most successful examples is the application of nitrile hydratase (NHase) to convert nitriles into amides [1]. The main question is how to optimize it further for industrial purposes [2, 3]. Some NHases lose their activity in the product concentration from 20% to 40% [4]. The current variant, extracted from Pseudonocardia thermophila, works at 30% of product concentration but loses activity when a product concentration reaches 50%. In order to gain insight into the mechanism of this effect and to propose modifications in the enzyme (1IRE.pdb) we performed molecular dynamics simulations (3x200 ns for each solution, 300 K) with increasing concentration of acrylamide (0%, 20%, 50% m/m respectively). We were able to observe that acrylamide molecules enter the active center of the enzyme. We could clearly see changes in hydrogen-bond patterns, new distribution of salt bridges and some changes in the first solvation shell induced by the increasing amount of the catalytic product. The problem of industrial enzyme optimization is well suited for massive all- atom simulations, since much longer time scales are necessary to model fully conformational all enzymatic reaction steps, that happen above millisecond timescale and conformational changes that happen in the protein. Acknowledgement: This research is funded by IDUB N. Copernicus #MEMOBIT grant. ICNT UMK computer facilities are acknowledged. 1. Cheng, Z., Y. Xia, and Z. Zhou, Front in Bioeng Biotechnol, 2020. 8(352): p.1. 2. Cheng, Z., Peplowski L. et al., Molecules, 2020. 25(20): p. 4806. 3. Guo J., Berdychowska J., Peplowski L. et al., Int J Biol Macromol, 2021. 181: p. 444. 4. Yamada, H. and M. Kobayashi, Biosci Biotechnol Biochem, 1996. 60(9): p. 1391

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