ArticlePloS one2015
Analysing the Effect of Mutation on Protein Function and Discovering Potential Inhibitors of CDK4: Molecular Modelling and Dynamics Studies.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 69 citations in OpenAlex.
- CDK4/6 Inhibitors for Breast Cancer Therapy-A Review of Clinical Trials, Structural and Computational Approaches.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Repercussions of the Calpain Cleavage-Related Missense Mutations in the Cytosolic Domains of Human Integrin-β Subunits on the Calpain-Integrin Signaling Axis.International journal of molecular sciences · 2025Article
- Computational studies on the functional and structural impact of pathogenic mutations in enzymes.Protein science : a publication of the Protein Society · 2025Review
- In silico functional, structural and pathogenicity analysis of missense single nucleotide polymorphisms in human MCM6 gene.Scientific reports · 2024Article
- Overcoming Resistance in Cancer Therapy: Computational Exploration of PIK3CA Mutations, Unveiling Novel Non-Toxic Inhibitors, and Molecular Insights Into Targeting PI3Kα.Bioinformatics and biology insights · 2024Article
- Targeting Protein-Protein Interactions to Inhibit Cyclin-Dependent Kinases.Pharmaceuticals (Basel, Switzerland) · 2023Article
- PSnpBind-ML: predicting the effect of binding site mutations on protein-ligand binding affinity.Journal of cheminformatics · 2023Article
- In Silico Analyses of All STAT3 Missense Variants Leading to Explore Divergent AD-HIES Clinical Phenotypes.Evolutionary bioinformatics online · 2023Article
- Seafood Paramyosins as Sources of Anti-Angiotensin-Converting-Enzyme and Anti-Dipeptidyl-Peptidase Peptides after Gastrointestinal Digestion: A Cheminformatic Investigation.Molecules (Basel, Switzerland) · 2022Article
- The Research Progress of Bufalin in the Treatment of Hepatocellular Carcinoma.OncoTargets and therapy · 2022Review
- Predicting Genetic Variation Severity Using Machine Learning to Interpret Molecular Simulations.Biophysical journal · 2021Article
- Emerging mutations in envelope protein of SARS-CoV-2 and their effect on thermodynamic properties.Informatics in medicine unlocked · 2021Article
- Pyrazinamide resistance of novel mutations inRSC advances · 2020Article
- Designing a new bispecific tandem single-chain variable fragment antibody against tumor necrosis factor-α and interleukin-23 using in silico studies for the treatment of rheumatoid arthritis.Journal of molecular modeling · 2020Article
- Article
- Structural and free energy landscape of novel mutations in ribosomal protein S1 (rpsA) associated with pyrazinamide resistance.Scientific reports · 2019Article
- Application of Computational Biology and Artificial Intelligence Technologies in Cancer Precision Drug Discovery.BioMed research international · 2019Review
- Novel ligand-based docking; molecular dynamic simulations; and absorption, distribution, metabolism, and excretion approach to analyzing potential acetylcholinesterase inhibitors for Alzheimer's disease.Journal of pharmaceutical analysis · 2018Article
- In silico mutational analysis and identification of stability centers in human interleukin-4.Molecular biology research communications · 2018Article
- A profound computational study to prioritize the disease-causing mutations in PRPS1 gene.Metabolic brain disease · 2018Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The cyclin-dependent kinase 4 (CDK4)-cyclin D1 complex plays a crucial role in the transition from the G1 phase to S phase of the cell cycle. Among the CDKs, CDK4 is one of the genes most frequently affected by somatic genetic variations that are associated with various forms of cancer. Thus, because the abnormal function of the CDK4-cyclin D1 protein complex might play a vital role in causing cancer, CDK4 can be considered a genetically validated therapeutic target. In this study, we used a systematic, integrated computational approach to identify deleterious nsSNPs and predict their effects on protein-protein (CDK4-cyclin D1) and protein-ligand (CDK4-flavopiridol) interactions. This analysis resulted in the identification of possible inhibitors of mutant CDK4 proteins that bind the conformations induced by deleterious nsSNPs. Using computational prediction methods, we identified five nsSNPs as highly deleterious: R24C, Y180H, A205T, R210P, and R246C. From molecular docking and molecular dynamic studies, we observed that these deleterious nsSNPs affected CDK4-cyclin D1 and CDK4-flavopiridol interactions. Furthermore, in a virtual screening approach, the drug 5_7_DIHYDROXY_ 2_ (3_4_5_TRI HYDROXYPHENYL) _4H_CHROMEN_ 4_ONE displayed good binding affinity for proteins with the mutations R24C or R246C, the drug diosmin displayed good binding affinity for the protein with the mutation Y180H, and the drug rutin displayed good binding affinity for proteins with the mutations A205T and R210P. Overall, this computational investigation of the CDK4 gene highlights the link between genetic variation and biological phenomena in human cancer and aids in the discovery of molecularly targeted therapies for personalized treatment.
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