Conformational Ensembles from Experimental Data and Computer Simulations

Conformational Ensembles from Experimental Data and Computer Simulations

Poster Abstracts

21-POS Board 21 Molecular-level Computer Simulations on the Self-assembled Peptides with Catalytic Activity Ruiheng Song, Guixiang Zeng, Wenfei Li, Hao Dong , Wei Wang. Nanjing University, Nanjing, China. Molecular self-assembly is ubiquitous in nature. Exploiting the principles of self-assembly could help people to create new materials with novel structures and functions. Amyloid fibrils made up with self-assembled short peptides have well-defined structures, which are able to form functional motif. In this work, we employed multi-scale molecular simulations to study amyloid- forming short peptides, which were reported to have remarkable activity to mimic the carbonic anhydrase. The building block is a 7-peptide with alternate hydrophobic and hydrophilic residues: the hydrophobic side-chains are able to have stable packing interactions with each others, and the hydrophilic histidine side-chains is capable of forming active sites for the catalytic reactions. Firstly, we explored the aggregation of peptides into organized structure as a consequence of hydrogen bonding and hydrophobic packing interactions among the subunits. Molecular simulations suggested that the sequence of the peptide greatly affects the pattern of the assembled structure, and therefore influences its catalytic activity. Based on the self- organized structure, we did systematic conformational searching on the rotamer library of histidine side-chain which are exposed to the solvent molecules, and identified two new coordination forms which are different from the structure in the active site of carbonic anhydrase. We further explored the atomic mechanism of the catalytic reaction taking place at the interface, compared it with the reaction happening at the active site of carbonic anhydrase, and proposed how to improve the catalytic activity of the artificial material.

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