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This study prioritized lung cancer-related targets using the HERBGAT framework based on graph attention networks (GAT). High-quality PDB structures were retrieved, and diffusion-generative docking was performed to construct complex conformations and assess their confidence levels. Molecular dynamics simulations of representative complexes were conducted over 200 ns, and binding free energies were estimated using the MM\/PBSA method. The pharmacokinetic characteristics of the bioactive compounds were evaluated using Swiss ADME and PreADMET computational tools, and density functional theory (DFT) analysis using ORCA software was combined to explore their electronic structure and properties. In this study, the potential targets of Pinellia ternata highly overlap with lung cancer pathological genes, with FGFR4, CDK2, JAK2, KDR, PAK4, PTK2 and PDGFRA being the core. Baicalein exhibits a conserved binding mode of \u201chinge hydrogen bond-aromatic interlayer-hydrophobic groove\u201d at targets such as PTK2\/KDR\/JAK2. Energy decomposition indicates that van der Waals forces and nonpolar solvation are the main thermodynamic driving forces for complex formation. Density functional theory (DFT) analysis further reveals that the high electronic \u201csoftness\u201d of baicalein and its sensitive response to the environment in terms of frontier orbitals and electrostatic potential may be related to its high affinity, which is ubiquitous in different pockets. This study provides a computational chain of evidence for the intervention of Pinellia ternata\u2019s active ingredient on lung cancer-related targets. The well-defined cross-target migratory pharmacophore of baicalein, consistent energy and kinetics, and the oral pharmacodynamics of ADMET indicate that it can serve as a multi-target lead compound targeting the PTK2\/KDR migration-angiogenesis pathway, while also affecting JAK2 and CDK2. Given that the current evidence is based on in-silico predictions, further validation through target enzymology, binding thermodynamics, and cellular pathway experiments is needed.<\/jats:p>","DOI":"10.1371\/journal.pone.0349376","type":"journal-article","created":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T17:30:25Z","timestamp":1779125425000},"page":"e0349376","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["In-silico prediction of multi\u2011target mechanisms of Pinellia ternata phytochemicals in lung cancer: Evidence from a graph\u2011attention\u2011guided virtual screening and multi\u2011scale 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wavefunctions","volume":"325","author":"F Neese","year":"2000","journal-title":"Chem Phys Lett"},{"issue":"8","key":"pone.0349376.ref034","doi-asserted-by":"crossref","first-page":"082503","DOI":"10.1063\/5.0216272","article-title":"A comprehensive electron wavefunction analysis toolbox for chemists, Multiwfn","volume":"161","author":"T Lu","year":"2024","journal-title":"J Chem Phys"},{"issue":"5","key":"pone.0349376.ref035","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1002\/jcc.22885","article-title":"Multiwfn: a multifunctional wavefunction analyzer","volume":"33","author":"T Lu","year":"2012","journal-title":"J Comput Chem"},{"issue":"1","key":"pone.0349376.ref036","doi-asserted-by":"crossref","DOI":"10.1016\/0263-7855(96)00018-5","article-title":"VMD: visual molecular dynamics","volume":"14","author":"W Humphrey","year":"1996","journal-title":"J Mol 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Yang","year":"2020","journal-title":"Mol Cancer"},{"issue":"9","key":"pone.0349376.ref049","doi-asserted-by":"crossref","first-page":"3937","DOI":"10.1158\/0008-5472.CAN-08-4327","article-title":"Ligand-dependent platelet-derived growth factor receptor (PDGFR)-alpha activation sensitizes rare lung cancer and sarcoma cells to PDGFR kinase inhibitors","volume":"69","author":"U McDermott","year":"2009","journal-title":"Cancer Res"},{"issue":"1","key":"pone.0349376.ref050","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1186\/s12967-021-03088-7","article-title":"The role of PDGFRA as a therapeutic target in young colorectal cancer patients","volume":"19","author":"TW Kim","year":"2021","journal-title":"J Transl Med"},{"key":"pone.0349376.ref051","doi-asserted-by":"crossref","first-page":"105468","DOI":"10.1016\/j.compbiomed.2022.105468","article-title":"Phytochemicals-based targeting RdRp and main protease of SARS-CoV-2 using docking and steered molecular dynamic simulation: a promising therapeutic approach for Tackling COVID-19","volume":"145","author":"A Parihar","year":"2022","journal-title":"Comput Biol Med"},{"issue":"8","key":"pone.0349376.ref052","doi-asserted-by":"crossref","first-page":"1919","DOI":"10.1007\/s12033-023-00831-x","article-title":"Screening of potential inhibitors targeting the main protease structure of SARS-CoV-2 via molecular docking, and approach with molecular dynamics, RMSD, RMSF, H-Bond, SASA and MMGBSA","volume":"66","author":"AM da Fonseca","year":"2024","journal-title":"Mol Biotechnol"},{"issue":"1","key":"pone.0349376.ref053","first-page":"24","article-title":"Molecular optimization, docking, and dynamic simulation profiling of selective aromatic phytochemical ligands in blocking the SARS-CoV-2 S protein attachment to ACE2 receptor: an in silico approach of targeted drug designing","volume":"8","author":"D Dey","year":"2021","journal-title":"J Adv Vet Anim 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