MAPK1 variant linked to cervical disease in 300-person study; simulations predict stronger SCH772984 binding to mutant

A 300-person study in Khyber Pakhtunkhwa found that the MAPK1 rs1057519911 variant was associated with cervical disease, particularly among participants with human papillomavirus infection. The researchers combined a case-control genetic association analysis with molecular docking, molecular dynamics simulations and binding-energy calculations. The reported results link the variant to disease susceptibility and predict stronger binding of the inhibitor SCH772984 to the resulting E322K mutant protein, but they do not establish that the variant causes disease or that the compound is clinically effective.

The association analysis included 100 HPV-positive patients, 100 HPV-negative patients and 100 healthy controls. Genotypes were determined using the Tetra-ARMS PCR method. Among HPV-positive patients, the CT genotype was associated with higher odds of cervical disease, with an odds ratio of 15.77 and a 95% confidence interval of 6.80 to 36.54. The TT genotype showed a larger association, with an odds ratio of 180.95 and a wide 95% confidence interval of 37.99 to 861.93; both reported P values were below 0.001. At the allele level, the T allele was associated with HPV-negative disease, with an odds ratio of 8.73 and a 95% confidence interval of 5.28 to 14.44, and HPV-positive disease, with an odds ratio of 15.22 and a 95% confidence interval of 9.10 to 25.46. Both allele-level P values were also below 0.001.

The study describes rs1057519911 as an oncogenic missense variant that produces the E322K amino acid substitution in MAPK1. To model its possible effect on inhibitor binding, the researchers used molecular docking, 50-nanosecond molecular dynamics simulations and post-simulation analyses that included RMSD, RMSF, beta-factor, radius of gyration, solvent-accessible surface area and dynamic cross-correlation. SCH772984 was predicted to have the highest docking affinity for the mutant protein, at −9.7 kcal/mol, compared with −8.8 kcal/mol for wild-type MAPK1.

The computational analyses also predicted more favorable calculated binding of SCH772984 to MAPK1 E322K. Reported MM-GBSA binding energies were −73.18 kcal/mol for the mutant complex and −66.22 kcal/mol for wild type, while the corresponding MM-PBSA values were −76.72 and −61.83 kcal/mol. The abstract describes the mutant complex as more stable after simulation. These findings are model-based estimates rather than laboratory drug tests or clinical evaluations. The genetic sample was relatively small, and the broad confidence interval for the TT genotype indicates substantial statistical uncertainty. Overall, the results provide evidence of an association in the studied population and identify SCH772984 as a computationally promising candidate, without demonstrating a treatment benefit in patients.

Subject of Research: Association of the MAPK1 rs1057519911 variant with cervical disease and computational analysis of SCH772984 binding

Article Title: Integrative genomic and biophysics analysis of MAPK1 rs1057519911 in cervical cancer: genetic association and therapeutic implications

Article References: Hassan, N., Ullah, A., Khan, N. U., Jan, Z., Ahmad, W., Albasher, G., & Al Sultan, N. (2026). Integrative genomic and biophysics analysis of MAPK1 rs1057519911 in cervical cancer: genetic association and therapeutic implications. BMC Cancer. https://doi.org/10.1186/s12885-026-16946-8

Image Credits: AI Generated

DOI: 10.1186/s12885-026-16946-8

Keywords: MAPK1, cervical cancer, HPV infection, genetic association, rs1057519911, E322K mutation, SCH772984, molecular docking, molecular dynamics, case-control study, Integrative, genomic