Fluorinated phospholipid analogs Edelfosine and Ilmofosine drug reveal expressive potential as antineoplastic factors though targeted interaction with heat shock protein (HSP70KDa1A), an essential mediator in cancer pathophysiology. Using evolved computational approaches, this research evaluated their ADMET (absorption, distribution, metabolism, excretion and toxicity) profiles receptor binding affinities and molecular dynamics. Molecular docking discernible vigorous interactions with Edelfosine drug displaying greater binding stability and consistent hydrogen bonding as confirmed by 100 ns molecular dynamics simulations. Comparative interpretation emphasized Edelfosine drug enhanced pharmacokinetic properties depicted by lower RMSD values, stable solvent-accessible surface area and reduced structural fluctuations relative to Ilmofosine drug. Functional annotation and phylogenetic investigation affirmed the evolutionary conservation and pivotal biological function of heat shock protein (HSP70KDa1A). These findings position Edelfosine drug as a promising candidate for targeted cancer therapy appropriated further experimental validation to elucidate its mechanisms of action and therapeutic efficacy.

Alzheimer's disease (AD), the primary cause of dementia and lacks potent therapeutic interventions. Natural biosurfactants containing Surfactin and Rhamnolipid, with neuroprotective capability and anti-inflammatory, extend favorable multi-target approaches. This study examined the therapeutic potential of Surfactin and Rhamnolipid against Alzheimer's disease operating network pharmacology and molecular docking to manifest their multi-target pathways. Network pharmacology was devoted to investigate Alzheimer's comparable targets of Rhamnolipid and Surfactin, observed by enrichment and network assay. Molecular docking and molecular dynamics simulations were then conducted to measure drug-target interactions and stability. Network pharmacology recognized 87 overlapping targets of Rhamnolipid and Surfactin with Alzheimer's disease, with hub genes involving CASP3, SRC, CTNNB1, HSP90AA1 and STAT3. GO and KEGG assessment identified enhancement in pathways related to synaptic signaling, immune regulation, kinase activity, and neuroinflammation. Docking explorations illustrated Rhamnolipid exhibited strong binding affinities, distinctly with 1BYQ (-11.1 kcal/mol), 7SEO (-9.1 kcal/mol), and 2SRC (-9.0 kcal/mol) while Surfactin confirmed weaker interactions. Molecular dynamics simulations (MD) affirmed stable complexes, with the Rhamnolipid CASP3 complex revealing the highest conformational stability. These findings indicate that biosurfactants, especially Rhamnolipid, exert neuroprotective effects against Alzheimer's disease through multi-target and multi-pathway functions. Their strong binding to crucial Alzheimer disease related proteins and stable interactions in dynamic simulations highlight their potential therapeutic agents, validating promote experimental validation.

Background: KRAS is among the most frequently mutated oncogenes in pancreatic, colorectal, and lung cancers, yet the structural and dynamic mechanisms by which specific coding variants alter its function remain poorly understood. This study employs an extensive in-silico protocol to identify the most detrimental non-synonymous single nucleotide polymorphisms (nsSNPs) within the KRAS gene. Objective: To identify and describe pathogenic non-synonymous single nucleotide polymorphisms (nsSNPs) in KRAS and elucidate their atomistic effects on structure, stability, and potential oncogenic initiation. Methods: A total of 173 nsSNPs were screened operating an integrated computational workflow combining pathogenicity prediction, evolutionary conservation assay, high-resolution structural modeling, molecular docking, atomistic molecular dynamics simulations, post-translational modification mapping, and protein–protein interaction assessment. Results: Four high-impact variants (L79P, A130P, G138E, and F141L) were determined as the most deleterious. Simulations revealed distinct perturbations in conformational stability (RMSD), residue flexibility (RMSF), hydrogen bonding patterns, and binding energetics compared with the wild type, signifying mutation-induced destabilization and potential impairment of KRAS regulatory function. Notably, these variants are primarily associated with colorectal, pancreatic, and lung cancers, underscoring their clinical significance. Conclusion: This integrative examination provides mechanistic insightinto how specific KRAS variations may prompt oncogenic activation. The identified alterations represent high-priority targets for experimental confirmation, illuminating the power of computational techniquesin linking sequence variationand functional consequence in cancer biology.

Toll-Interacting Protein ( TOLLIP ) serves as key adaptor molecule in innate immune signaling, modulating toll-like receptors (TLRs) and interleukin-1 (IL-1) pathway. Despite its central role, the functional impact of non-synonymous single nucleotide polymorphism (nsSNPs) on TOLLIP remains unclear. Using an integrated computational approach, we screened 150 TOLLIP nsSNPs through consensus predictive tools including PROVEAN, PANTHER, SNPs & GO and SIFT. This approach identified four high confidence deleterious variants (R28Q, T40M, P59L, and R200C) with strong potential to compromise TOLLIP protein stability and function. Structural analysis and energy minimization suggested subtle confirmation changes and destabilizing effect, while TM-align displayed preservation of overall folding (TM-score >0.99, RMSD <0.54 Å). Evolutionary conservation, phylogenetic analysis, and protein-protein interaction (PPI) analysis underscored the functional and confirmation importance of these residues. Notably, molecular docking and dynamic simulations revealed that T40M and R200C variants significantly enhance binding affinity for the Afimetoran. Additionally, molecular dynamics (MD) simulations highlighted the altered flexibility, solvent accessibility and modified hydrogen bonds in mutant proteins structure, suggesting potential mechanisms for functional disruption. Collectively, these findings elucidate the structural and functional consequences of nsSNPs on TOLLIP protein stability, and provide a rational base for targeted therapeutic strategies in immune related diseases.