Fassi, Enrico M.A. Sgrignani, Jacopo D'Agostino, Gianluca Cecchinato, Valentina Garofalo, Maura Grazioso, Giovanni Uguccioni, Mariagrazia Cavalli, Andrea 2019-06-21 High-mobility Group Box 1 (HMGB1) is an abundant protein present in all mammalian cells and involved in several processes. During inflammation or tissue damage, HMGB1 is released in the extracellular space and, depending on its redox state, can form a heterocomplex with CXCL12. The heterocomplex acts exclusively via the chemokine receptor CXCR4 enhancing leukocyte recruitment. Here, we used multi-microsecond molecular dynamics (MD) simulations to elucidate the effect of the disulfide bond on the structure and dynamics of HMGB1. The results of the MD simulations show that the presence or lack of the disulfide bond between Cys23 and Cys45 modulates the conformational space explored by HMGB1, making the reduced protein more suitable to form a complex with CXCL12. application/pdf https://n2t.net/ark:/12658/srd1319123 https://susi.usi.ch/global/documents/319123 https://susi.usi.ch/documents/319123/files/Fassi_Comput_Struct_Biol_2019.pdf eng info:eu-repo/semantics/altIdentifier/doi/10.1016/j.csbj.2019.06.020 info:eu-repo/semantics/altIdentifier/ark/12658/srd1319123 info:eu-repo/semantics/openAccess CC BY-NC-ND Computational and structural biotechnology journal. - 2019, vol. 17, p. 886-894 HMGB1 CXCL12 Molecular dynamics Protein-protein docking Conformational ensemble info:eu-repo/classification/udc/57/59 Oxidation state dependent conformational changes of HMGB1 regulate the formation of the CXCL12/HMGB1 heterocomplex http://purl.org/coar/resource_type/c_6501