Biophysical Society Thematic Meeting | Hamburg 2022

Biophysics at the Dawn of Exascale Computers

Poster Abstracts

53-POS Board 53 OPTIMAL PROTEIN SEQUENCE DESIGN MITIGATES MECHANICAL FAILURE IN SILK BETA-SHEET NANOCRYSTALS

Paras Verma 1 ; Biswajit Panda 2 ; Kamal P Singh 2 ; Shashi B Pandit 1 ; 1 IISER Mohali, Department of Biological Sciences, Mohali, India 2 IISER Mohali, Department of Physical Sciences, Mohali, India

Spider silk fiber possesses exceptional mechanical strength attributes such as high tensile strength, toughness, and elasticity in tensile loading. Previous experimental and computational studies showed that these extraordinary mechanical properties results mostly from a) hierarchical arrangement of antiparallel β - sheet nanocrystals in disordered matrix, b) corresponding β -strand length and, c) H-bond interactions among them. However, the dependence of mechanical properties of silk nanocrystal on its motifs remains largely unexplored despite these studies. To investigate the significance of β -sheet sequence motifs, we modeled various representative amino acid homopolymers on said β -sheet geometry and analysed their impact and mechanical properties. We chose amino acid sequences having small (Gly/Ala/Ala-Gly) or polar (Thr/Asn) or hydrophobic (Ile/Val) side chains and used Steered Molecular Dynamics (SMD) to pull their central β -strand. Multiple SMD pull-out simulations showed that homopolymers of naturally occurring sequence motifs (Ala/Ala-Gly) have superior mechanical properties than other modeled sequence motifs. Surprisingly, the enhanced side-chain interactions in homo(poly)- polar/hydrophobic amino acid models were unable to augment backbone hydrogen bond cooperativity to increase mechanical strength. Thereafter, we analyzed the hydrogen bond and β - strand pull dynamics of modeled nanocrystals, and this suggested that nanocrystal of pristine silk sequences most likely achieve superior mechanical strength by optimizing side chain interactions, inter-sheet packing, and main-chain H-bond interactions. This advanced our understanding of sequence-dependent mitigating factors and their variations in β -sheet rupture mechanisms. Conclusively, our study suggested that β -sheet nanocrystal's default sequence while being evolutionary optimized is also a key factor in determining nanomechanical properties of silk and this study also provides insight into the silk’s molecular design principle with implications in the genetically modified artificial synthesis of silk-like biomaterials.

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