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Precision spatiotemporal analysis of large-scale compound-protein interactions through molecular dynamics simulation
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Precision spatiotemporal analysis of large-scale compound-protein interactions through molecular dynamics simulation

Shigeyuki Matsumoto, Yuta Isaka, Ryo Kanada, Biao Ma, Mitsugu Araki, Shuntaro Chiba, Atsushi Tokuhisa, Hiroaki Iwata, Shoichi Ishida, Yoshinobu Akinaga, …
PNAS nexus, 卷.4(3), 頁.pgaf094
01/03/2025
PMID: 40161316
Web of Science ID: WOS:001482374400001

摘要

Multidisciplinary Sciences Science & Technology Science & Technology - Other Topics Social Sciences Social Sciences - Other Topics Social Sciences, Interdisciplinary
Biological systems are composed of and regulated by intricate and diverse biomolecular interactions. Experimental and computational approaches have been developed to elucidate the mechanisms of these interactions; however, owing to cost, time, and accuracy issues, large-scale spatiotemporal analyses of molecular pairs remain challenging. Thus, the molecular recognition mechanisms underlying these diverse interactions remain unclear. We successfully simulated the large-scale molecular dynamics (MD) of 4,275 protein-compound pairs by combining a method to accelerate the MD simulations with the supercomputer Fugaku. Our spatiotemporal analysis of generated big MD data revealed universal features underlying molecular recognition and binding processes. This study expands our understanding of the concept of MD simulations from a technique to investigate the dynamic properties of individual protein-drug pairs to an approach to perform large-scale spatiotemporal analysis and compound screening. This study opens an avenue in biological research for subsequent drug discovery.

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https://doi.org/10.1093/pnasnexus/pgaf094檢視
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