biostudies-literatureRaj NMinistry of Science and Technology, Taiwan3688-3696https://www.ebi.ac.uk/biostudies/studies/S-EPMC8966636biostudies-literatureUnknown13(13)A protein's adaptive response to its substrates is one of the key questions driving molecular physics and physical chemistry. This work employs the recently developed structure-mechanics statistical learning method to establish a mechanical perspective. Specifically, by mapping all-atom molecular dynamics simulations onto the spring parameters of a backbone-side-chain elastic network model, the chemical moiety specific force constants (or mechanical rigidity) are used to assemble the rigidity graph, which is the matrix of inter-residue coupling strength. Using the S1A protease and the PDZ3 signaling domain as examples, chains of spatially contiguous residues are found to exhibit prominent changes in their mechanical rigidity upon substrate binding or dissociation. Such a mechanical-relay pChemical scienceStructure-mechanics statistical learning uncovers mechanical relay in proteins.PMC8966636110-2113-M-A49-024Yang HRaj NClick THChu JWfalseStructure-mechanics statistical learning uncovers mechanical relay in proteins.A protein's adaptive response to its substrates is one of the key questions driving molecular physics and physical chemistry. This work employs the recently developed structure-mechanics statistical learning method to establish a mechanical perspective. Specifically, by mapping all-atom molecular dynamics simulations onto the spring parameters of a backbone-side-chain elastic network model, the chemical moiety specific force constants (or mechanical rigidity) are used to assemble the rigidity graph, which is the matrix of inter-residue coupling strength. Using the S1A protease and the PDZ3 signaling domain as examples, chains of spatially contiguous residues are found to exhibit prominent changes in their mechanical rigidity upon substrate binding or dissociation. Such a mechanical-relay p2022-01-01T00:00:00Z2022 Mar2026-05-09T20:10:23.083Z2025-04-05T09:59:21.221ZS-EPMC89666363543291110.1039/d1sc06184d