Multiscale modeling of collagen for revealing structural, mechanical, and dynamic properties related to aging and human diseases

• Constructed molecular models of wild-type and Gly-substituted tropocollagens to determine stiffnesses in MD simulations; 

• Created Markov state models to analyze the unwound structural states in the mutated regions of these tropocollagen models; 

• Investigated the vibration modes of collagen models by normal mode analysis using the anisotropic network method;

• Developing a coarse-grained model of tropocollagens, focusing on accurately simulating sliding and stretching forces (in progress);

• Writing a software package designed to construct coarse-grained collagen fibril models, featuring customizable tropocollagen assembly and variable diameters (in progress);

• Investigating the stress-strain response and structural characteristics of collagen fibrils under varied loading conditions and cross-link densities (in progress).

Outcomes and impact: 

• Identified remarkable differences in stiffnesses and dynamics for mutated collagens attributed to the unwound structural characteristics after mutations; 

• Revealed molecular impact of genetic diseases on collagen functions for future development of targeted molecular therapies.

Shi, H. & Yeo, J.† (2024, in preparation). Investigating energy dissipation and inelastic response in collagen fibrils under cyclic loading: a molecular dynamics investigation.

Shi, H., Zhao, L., Zhai, C., & Yeo, J.† (2021). Specific osteogenesis imperfecta-related Gly substitutions in type I collagen induce distinct structural, mechanical, and dynamic characteristics. Chemical Communications, 57(91), 12183-12186. https://doi.org/10.1039/D1CC05277B Featured in: 2021 Emerging Investigators