Cover Story：Objective Allostery plays important roles in regulating protein biological functions. How to effectively identify the allosteric signal transduction pathway and the related key residues from the tertiary structure of proteins is a hot scientific problem in the research field of protein structure-function relationship.Methods In the present work, a method based on elastic network model (ENM) combined with force distribution calculation was used to investigate the response of proteins to the external loading forces, and then the allosteric pathway and associated key residues in proteins were identified based on the analysis of internal force distribution. In this method, external forces were exerted on the allosteric site of the protein, and then the deformations and internal force distributions within the protein in response to the external loading forces were analyzed. Based on these analyses, the key sites that are coupled with the deformation of the force-loading region were identified, and the transduction pathway of the force signals in the protein was obtained.Results By using the proposed method, two proteins, the human phosphoglycerate kinase (hPGK) and protein tyrosine phosphatase (PTP) PDZ2 domain, were investigated to identify the allosteric pathway and the related key residues in the systems. For hPGK, two allosteric pathways were identified, which mediate the transduction of force signals from the substrate binding site to the hinge region of the protein. For PTP PDZ2, two long-range allosteric pathways, from the ligand binding site to the distantly opposite side of the protein, were also successfully revealed. The calculation results are consistent with the experimental observations and the results obtained with molecular dynamics simulations.Conclusion This study provides an effective method for the identification of key residues and allosteric pathway in proteins.