ObjectivesThe SOCS1 gene is frequently mutated in primary Diffuse Large B-Cell Lymphoma (DLBCL) patients and is associated with a reduced survival rate. Using various computational techniques, the current study aims to identify Single Nucleotide Polymorphisms (SNPs) in the SOCS1 gene that are associated with the mortality rate of DLBCL patients. This study also evaluates the effects of SNPs on the structural instability of the SOCS1 protein in DLBCL patient. MethodsThe cBioPortal webserver was used for mutations and determining how the SNP mutations affect the SOCS1 protein with various algorithms (PolyPhen-2.0, Provean, PhD-SNPg, SNPs&GO, SIFT, FATHMM, Predict SNP and SNAP). Five webservers (I-Mutant 2.0, MUpro, mCSM, DUET and SDM) were used for protein instability and the conserved status and were also predicted through different tools (ConSurf, Expasy, SOMPA). Lastly, MD simulations were run on the two chosen mutations (S116N and V128G) using GROMACS 5.0.1 to study how the mutations change the structure of SOCS1. ResultsAmong the 93 SOCS1 mutations detected in DLBCL patients, nine mutations were found to have a detrimental effect (damaging/deleterious/pathogenic/altered) on the SOCS1 protein. All the nine selected mutations are in the conserved region and four are on the extended strand site, four on the random coil site and one on the alpha helix position of the secondary protein structure. After anticipating the structural effects of these nine mutations, two were chosen (S116N and V128G) based on mutational frequency, location within the protein, structural effect (primary, secondary and tertiary) on stability and conservation status within the SOCS1 protein. The simulation of a 50 ns time interval revealed that the Rg value of S116N (2.17 nm) is higher than that of WT (1.98 nm), indicating a loss of structural compactness. In the case of the RMSD value, this mutated type (V128G) shows more deviation (1.54 nm) in comparison to the wild-type (2.14 nm) and another mutant type (S116N) (2.12 nm). The average RMSF values of wild-type and mutant types (V128G and S116N) were 0.88 nm, 0.49 nm, and 0.93 nm, respectively. The RMSF result shows that the mutant V128G structure is more stable than the wild-type and mutant S116N structures. ConclusionBased on all these computational predictions, this study finds that certain mutations, particularly S116N, have a destabilising and robust effect on the SOCS1 protein. These results can be used to learn more about the importance of SOCS1 mutations in DLBCL patients and to develop new ways to treat DLBCL.