Chemical cross-linking of proteins coupled with mass spectrometry analysis (CXMS) is to covalently link two protein residues with cross-linkers and then to identify the inter-linked peptides using mass spectrometry method1.CXMS is widely applied in protein chemistry research for providing valuable spatial information for protein structure prediction and protein-protein interface identification2.Although several computational methods have been developed to predict and validate CXMS results, these methods are still suffering certain limitations.Therefore, we developed a new method based on molecular dynamics (MD) simulation (designated XLMD).