Abstract
Polymorphisms in immune-related proteins and viral spike proteins are high and complicate host-virus interactions. Therefore, diversity analysis of such protein structures is essential to understand the mechanism of the immune system. However, experimental methods, including X-ray crystallography, nuclear magnetic resonance, and cryo-electron microscopy, have several problems: (i) they are conducted under different conditions from the actual cellular environment, (ii) they are laborious, time-consuming, and expensive, and (iii) they do not provide information on the thermodynamic behaviors. In this paper, we propose a computational method to solve these problems by using MD simulations, persistent homology, and a Bayesian statistical model. We apply our method to eight types of HLA-DR complexes to evaluate the structural diversity. The results show that our method can correctly discriminate the intrinsic structural variations caused by amino acid mutations from the random fluctuations caused by thermal vibrations. In the end, we discuss the applicability of our method in combination with existing deep learning-based methods for protein structure analysis.