Molecular Dynamics Study of the Structure and Mechanical Properties of Spider Silk Proteins

Zhaoting Yuan; Bohuan Fang; Qixin He; Hao Wei; Haiming Jian; Lujia Zhang

doi:10.1021/acs.biomac.4c01398

Molecular Dynamics Study of the Structure and Mechanical Properties of Spider Silk Proteins

Biomacromolecules. 2025 Jan 2. doi: 10.1021/acs.biomac.4c01398. Online ahead of print.

Authors

Zhaoting Yuan¹, Bohuan Fang², Qixin He³, Hao Wei², Haiming Jian⁴, Lujia Zhang^{1

5}

Affiliations

¹ Shanghai Engineering Research Center of Molecular Therapeutics & New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China.
² Department of Micro/Nano Electronics, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.
³ State Key of Bioreactor Engineering, New World Institute of Biotechnology, East China University of Science and Technology, Shanghai 200237, China.
⁴ School of Life Science and Technology, Inner Mongolia University of Science and Technology, Baotou 014010, China.
⁵ NYU-ECNU Center for Computational Chemistry at NYU Shanghai, Shanghai 200062, China.

PMID: 39748448
DOI: 10.1021/acs.biomac.4c01398

Abstract

Spider silk is renowned for its exceptional toughness, with the strongest dragline silk composed of two proteins, MaSp1 and MaSp2, featuring central repetitive sequences and nonrepetitive terminal domains. Although these sequences to spider silk's strength and toughness, the specific roles of MaSp1 and MaSp2 at the atomic level remain unclear. Using AlphaFold3 models and molecular dynamics (MD) simulations, we constructed models of MaSp1 and MaSp2 and validated their stability. Steered molecular dynamics (SMD) simulations showed that MaSp2 resists lateral stretching, whereas MaSp1 exhibited better extensibility. During longitudinal stretching, MaSp1 formed cavities, whereas MaSp2 stretched uniformly. Hydrogen bonds involving GLN and SER in MaSp1 were strong, whereas those involving Tyr307 were prone to breakage, potentially weakening toughness. These results indicate that MaSp1 enhances extensibility, whereas MaSp2 imparts greater toughness. This study offers key molecular insights into spider silk's strength, informing the design of artificial fibers.