Journal of Biomolecular Structure & Dynamics最新文献

{"title":"Comparative analysis of three-pillared and four-pillared synthetic glucose receptor using molecular dynamics simulations: a case study.","authors":"Rajesh Kondabala, Vijay Kumar, Amjad Ali","doi":"10.1080/07391102.2025.2551193","DOIUrl":"https://doi.org/10.1080/07391102.2025.2551193","url":null,"abstract":"<p><p>The advancement of computational molecular modeling has significantly enhanced the development of synthetic glucose receptors, addressing one of the most challenging problems in glucose recognition. This study explores the design and analysis of both three-pillared and four-pillared synthetic glucose receptors. Using polar (1,2-Bis(3-methylureido)benzene) pillars combined with benzene, biphenyl, and phenanthrene fragments as apolar surfaces, we have designed novel receptors. Our molecular dynamics simulations reveal that benzene is the most favorable apolar fragment for creating synthetic glucose receptors. Further simulations incorporating Mesitylene, Trimethylmesitylene, Triethylmesitylene, and Triptopylmesitylene as apolar fragments with (1,2-Bis(3-methylureido)benzene) polar pillars demonstrate that receptors with Triethylmesitylene and Triptopylmesitylene exhibit stable conformations. Synthetic glucose receptors represent the future of therapeutics for glucose-related disorders and conditions. These receptors have wide-ranging applications, including functioning as glucose carriers and glucose extractors. The 3D structures of the receptors were constructed using the 3D Builder tool, followed by energy minimization <i>via</i> the MacroModel application. The glucose-receptor interaction poses were predicted using the GLIED tool. Calculations were performed using the Berendsen thermostat and barostat. Molecular dynamics (MD) simulations were conducted with the Langevin ensemble method, utilizing GPU-based DESMOND software with the OPLS2005 force field and the TIP3P solvent model.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-10"},"PeriodicalIF":2.4,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144955640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular insights into PARP1 activation: structural dynamics of DNA, NAD+, and zinc‑mediated allosteric regulation.","authors":"Areeba Munir, Noorulain Naseer, Taskeen Koser, Rana Rehan Khalid","doi":"10.1080/07391102.2025.2551909","DOIUrl":"https://doi.org/10.1080/07391102.2025.2551909","url":null,"abstract":"<p><p>PARP1 serves as a crucial protein for preserving genomic stability, especially in BRCA1/2-mutant cancers that lack homologous recombination repair. In response to DNA breaks, PARP1 triggers an allosteric response that communicates to its catalytic domain, initiating the synthesis of poly (ADP-ribose) from NAD+. In this study, we used RMSF, hydrogen bond, hydrophobic, and MMPBSA analyses to construct an interface-specific map of PARP1 activation, revealing how DNA, Zn ions, and NAD+ act at each domain interface to drive activation. Our findings show that DNA initiates allosteric signaling, Zn ions and NAD+ strengthen activating interfaces and weaken inhibitory contacts. We found that PARP1 recognizes DNA damage through its ZF1, ZF3, and WGR domains with Zn ions at ZF1 stabilizing DNA binding. Allosteric contacts arose at the ZF1-ZF3 interface strengthened by DNA, ZF3-WGR interface reinforced by Zn ions, and ZF1-WGR interface stabilized by both DNA and Zn ions. This allosteric communication, alongside NAD+, induced a conformational shift in the HD domain enhancing WGR-HD and ZF3-HD interactions and destabilizing HD-ART. This movement, opened the catalytic pocket for NAD+ binding, promoting PARylation. Our study shows that full PARP1 activation requires the PARP1-DNA-Zn-NAD+ complex. These findings advance understanding of PARP1 and may aid development of targeted inhibitors for synthetic lethality-based cancer therapy.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-27"},"PeriodicalIF":2.4,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144955711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights into cannabinoid-HSA interactions: spectroscopic analysis and molecular docking for binding site characterization.","authors":"Sogol Meknatkhah, Mohammad Reza Ashrafi-Kooshk, Hossein Lanjanian, Jahan B Ghasemi, Gholam Hossein Riazi","doi":"10.1080/07391102.2025.2551174","DOIUrl":"https://doi.org/10.1080/07391102.2025.2551174","url":null,"abstract":"<p><p>Cannabinoids are increasingly recognized for their therapeutic potential, yet their pharmacokinetics remain poorly understood due to their high hydrophobicity and complex interactions with plasma proteins. Human serum albumin (HSA), the principal drug carrier in blood, critically influences the distribution, bioavailability, and efficacy of lipophilic compounds. In this study, we comprehensively investigated the binding interactions between HSA and six major cannabinoids (THC, CBD, CBC, CBG, THCV, and CBDV) using fluorescence spectroscopy, synchronous fluorescence scanning (SFS), circular dichroism (CD) spectroscopy, and molecular docking simulations. Fluorescence quenching analysis revealed a static quenching mechanism, supported by quenching rate constants (<i>K</i>_b) exceeding diffusion limits. Temperature-dependent studies and van't Hoff analysis indicated that the interactions were driven primarily by hydrophobic forces, as evidenced by positive entropy and enthalpy changes. CD spectral analysis showed that most cannabinoids induced minimal or stabilizing effects on HSA's α-helical structure, with the exception of CBDV and CBG, which caused more pronounced, concentration-dependent secondary structure changes. Molecular docking localized the binding sites predominantly within Sudlow's sites I, involving key hydrophobic residues such as Ile, Leu, Val and Ala. Together, these findings provide new molecular insights into the transport properties of cannabinoids and highlight the role of albumin in modulating their pharmacokinetic profiles, offering valuable guidance for therapeutic drug design and delivery strategies.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-17"},"PeriodicalIF":2.4,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144955706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the functional and structural impacts of high-risk nsSNPs in human <i>BMP15</i> and <i>GDF9</i> genes associated with premature ovarian failure: an <i>in silico</i> approach.","authors":"Leila Navapour, Zeinab Jamali, Hojat Ghasemnejad-Berenji, Navid Mogharrab, Sahar Rezaei Arablouydareh, Sonia Sadeghpour, Abbas Jafari, Pourya Rokhsartalab Azar, Mortaza Taheri-Anganeh","doi":"10.1080/07391102.2025.2549782","DOIUrl":"https://doi.org/10.1080/07391102.2025.2549782","url":null,"abstract":"<p><p>Premature ovarian failure (POF) is a complex reproductive disorder characterized by the early loss of ovarian function. Two closely related members of the transforming growth factor-β (TGF-β) superfamily, bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9) have been implicated in its pathogenesis. In this study, we investigated the potential pathogenicity of 429 non-synonymous SNPs (nsSNPs) in <i>GDF9</i> and 290 nsSNPs in <i>BMP15</i> using an integrative bioinformatics approach. Multiple computational tools including SIFT, PolyPhen-2, PROVEAN, MutationAssessor, FATHMM, PhD-SNP, SNPs&GO, MutPred2, VEST-4, DDMut, INPS-3D, DDGun-3D and MAESTRO were employed to identify high-risk variants. As a result, three pathogenic variants in <i>GDF9</i> (C382R, C419Y and L430S) and three in <i>BMP15</i> (C291Y, C320G and C357R) were predicted to significantly reduce protein stability and function. Molecular dynamics simulation was performed to explore the structural alterations in GDF9 and BMP15 proteins induced by these variations. The MD results revealed that all the identified high-risk nsSNPs particularly C382R (GDF9) and C291Y (BMP15) triggered significant changes on the protein structure. The variants were found to less stable compared to the wild-type proteins which was associated with the increased local and overall flexibility, impaired hydrogen bond network and loss or distortion of β-sheet elements. These findings suggest a destabilizing effect that could lead to reduced structural integrity, impaired protein folding or functional deficiencies and ultimately contribute to the pathogenesis of these ovarian-related proteins.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-19"},"PeriodicalIF":2.4,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144955780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mutation studies on transmembrane protein sulphate permease for enhanced biohydrogen production in <i>Chlamydomonas reinhardtii:</i> a molecular dynamics simulation approach.","authors":"A Arun Kumar, Akhila S Hegde, Vinita V Bhat, Shravan R Shankar, Sasmita Sabat","doi":"10.1080/07391102.2025.2548421","DOIUrl":"https://doi.org/10.1080/07391102.2025.2548421","url":null,"abstract":"<p><p>Fossil fuel reserves are rapidly depleting, necessitating the need to find a promising alternative. Hydrogen is a clean and promising energy source with a significant energy yield and water as the only byproduct leading many to view it as a viable source of renewable energy. Despite traditional assessments for the techno-economic feasibility of biohydrogen not supporting its practical implementation, biologically produced hydrogen remains a more environmentally friendly and an efficient energy source. Recent studies have reported that low levels of sulphate permease (SulP) is said to increase hydrogen production. Mutation studies were carried out and molecular docking was performed for wild type and mutated sulphate permease with ligands that dampen its activity as reported in literature. Effect of mutation on SULP1 gene in <i>Chlamydomonas reinhardtii</i> was assessed using PredictSNP, I-Mutant 2.0, and SIFT. Sulphate permease being a transmembrane protein, CHARMM-GUI membrane builder module was used for solvent equilibration, lipid bilayer generation and proteins. Protein structures were harmonically restrained to maintain their initial positions and allow the solvent to equilibrate effectively. Molecular simulations were performed for wild & mutant types with ligands and assessed for RMSD, RMSF, intra- and inter-hydrogen bond interactions, Rg and SASA till 200 ns using GROMACs v.2016. The MMPBSA values were found to be -29.392 +/- 11.753 kJ/mol WT (Wild type) and -34.080 +/- 10.837 kJ/mol MT (Mutant type). Significant structural modification was inferred through the mutation approach.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-23"},"PeriodicalIF":2.4,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144955749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational insights into <i>PKCθ</i> non-synonymous SNPs: from structural changes to functional implications.","authors":"Amna Hafeez, Andleeb Farooq, Maria Shabbir, Yasmin Badshah, Naeem Mahmood Ashraf, Janeen H Trembley, Tayyaba Afsar, Ali Abusharha, Sameen Zafar, Suhail Razak","doi":"10.1080/07391102.2025.2550618","DOIUrl":"https://doi.org/10.1080/07391102.2025.2550618","url":null,"abstract":"<p><p>Single-nucleotide polymorphisms (SNPs) play a critical role in individual diversity, genome evolution, and susceptibility to diseases such as cancer and diabetes. This study focuses on the <i>PRKCQ</i> gene, encoding protein kinase C theta (<i>PKCθ</i>), a serine/threonine kinase belonging to the PKC family, involved in immune response and cancer progression. Pathogenicity assessment using multiple bioinformatic tools identified six highly pathogenic non-synonymous SNPs (nsSNPs), all predicted to be oncogenic (rs1838691533 R6W, rs145984477 P27L, rs1248923790 C29Y, rs1837738907 R145C, rs1837738573 R146W, rs1403981107 L495P). Structural predictions and domain analyses identified crucial functional regions in <i>PKCθ</i>, with specific variants located in domains essential for membrane binding and catalytic activity. Conservation profiling highlighted the evolutionary significance of these residues, indicating their critical roles in protein function. Stability analysis of selected nsSNPs demonstrated that most variations decrease protein stability, confirmed by various computational tools. Molecular dynamics (MD) simulations further showed that these variants significantly alter <i>PKCθ</i>'s conformation and stability, impacting its function. These findings underscore the importance of <i>PKCθ</i> in oncogenic signaling and highlight the potential for targeted therapies and personalised medicine approaches to address <i>PRKCQ-</i>associated diseases.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-20"},"PeriodicalIF":2.4,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144955660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biophysical, sequence and structural analysis of type 3 secretion system pilus protein HrpA of <i>Pseudomonas syringae</i>: insights into HrpA pili stability and assembly.","authors":"Naveen Arasakumar, Vikraam Loganathan, Ramanathan Natesh, Karthe Ponnuraj","doi":"10.1080/07391102.2025.2549436","DOIUrl":"https://doi.org/10.1080/07391102.2025.2549436","url":null,"abstract":"<p><p>Type 3 secretion system (T3SS) is an essential virulence system utilized by many gram-negative bacteria including <i>P. syringae</i> to deliver effector proteins into host cells. The extracellular, long, needle-like proteinaceous complex (pilus) of T3SS transports effectors. In <i>P. syringae</i>, HrpA, an 11 kDa protein assembles to form the pilus structure, whose structure and stability remain poorly understood. To address this, recombinant HrpA protein was prepared and carried out the biophysical characterization. The native PAGE and dynamic light scattering analysis showed higher-order oligomerization of rHrpA with hydrodynamic radii in the range of 1-1000 nm. Transmission Electron Microscopy revealed that rHrpA spontaneously forms needle-like filaments (∼8 nm in width and ∼129-300 nm in length) and also the aggregation of the filaments. CD spectroscopic analysis showed the predominantly helical nature of rHrpA. We examined the effects of detergents, denaturants, pH and temperature on rHrpA assemblies. Detergents such as SDS and sarkosyl effectively disrupted the oligomers, whereas urea and guanidine hydrochloride had no effect. The sequence analysis of HrpA from different pathovars of <i>P. syringae</i> revealed that, for the first time, two groups of HrpA proteins (108 aa and 113 aa) that are sequence-wise unrelated. Structural comparison of HrpA with animal filament proteins such as MxiH, PrgI and BsaL revealed that plant pilus structures could be highly flexible compared to animal filaments. This study contributes to our understanding of the T3SS pilus structure and its stability. The results of this study could lead to new approaches for T3SS pilus protein structure-function investigation.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-19"},"PeriodicalIF":2.4,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144955662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Binding interactions between ar-turmerone and human serum albumin: mechanistic and biophysical insights.","authors":"Nurul Jannah Mohd Asngari, Fazal Rehman, Saharuddin Bin Mohamad, Saad Tayyab, Khairul Azreena Bakar, Shevin Rizal Feroz, Syarifah Nur Syed Abdul Rahman, Siti Amalina Inche Zainal Abidin, Fathilah Abdul Razak, Adyani Azizah Abd Halim","doi":"10.1080/07391102.2025.2543359","DOIUrl":"https://doi.org/10.1080/07391102.2025.2543359","url":null,"abstract":"<p><p>Ar-turmerone, a major bioactive compound in <i>Curcuma purpurascens</i>, has been reported to exhibit anti-inflammatory, antiproliferative, antifungal, antioxidant, and anticancer properties. This study investigated its interaction with human serum albumin (HSA) using spectroscopic, microscopic, and computational approaches to characterize its binding properties, which are crucial for its distribution and transport in the bloodstream. Fluorescence spectroscopy showed a 34% decrease in HSA fluorescence intensity at 90 μM ar-turmerone, accompanied by a 2 nm blue shift, suggesting a transition of the protein's fluorophores' microenvironment to a slightly nonpolar state. Binding analysis indicated a moderate binding affinity (<i>K</i>_a = 1.79 ± 0.12 × 10⁴ M^-1) and a negative Gibbs free energy change (ΔG° = -6.03 ± 0.04 kcal/mol), indicating a spontaneous and energetically favorable binding process. Hypochromic effects near the Trp residue suggested a static interaction mechanism. Circular dichroism analysis confirmed that ar-turmerone did not induce major alterations in HSA's secondary and tertiary structures. Microscopic observations revealed slight modifications to the protein surface, suggesting the formation of protein aggregates. Both displacement studies and molecular docking results indicated that ar-turmerone primarily binds at the Site III (subdomain IB) of HSA. Molecular docking further suggested that this binding is stabilized through hydrogen bonding, hydrophobic interactions, and van der Waals forces. These findings provide insights into the binding dynamics of ar-turmerone with HSA, which may influence its transport, stability, and bioavailability. Understanding this interaction is essential for assessing its pharmacokinetic behavior, including transport, stability, bioavailability, which are critical for potential applications in drug delivery and therapeutic development.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-18"},"PeriodicalIF":2.4,"publicationDate":"2025-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144873380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amino acid osmolytes disrupting intradomain interactions reduce the amyloidogenicity of α-synuclein: studies with charged l-amino acids and their derivatives.","authors":"Archi Saurabh, Suraj Chauhan, Jogadhenu S S Prakash, N Prakash Prabhu","doi":"10.1080/07391102.2025.2543362","DOIUrl":"https://doi.org/10.1080/07391102.2025.2543362","url":null,"abstract":"<p><p>Aggregation of α-synuclein (α-syn) is a hallmark of Parkinson's and dementia with Lewy bodies pathogenesis. The high plasticity and lack of stable tertiary structure make α-syn more susceptible to its surrounding environment. Under stress conditions, small organic molecules known as osmolytes accumulate inside the cells. They affect the conformational states and fibrillation pathways of proteins. Here, the effects of eight different amino acid osmolytes (charged: l-glutamate, l-aspartate, l-lysine, l-arginine; amide side chains: l-glutamine, l-asparagine; and <i>N</i>-acetylated: <i>N</i>-acetyl-l-glutamic acid, <i>N</i>-acetyl-l-lysine) on the fibrillation of human α-synuclein were examined. Arginine and <i>N</i>-acetyl-l-lysine inhibited the fibrillation at concentrations above 0.2 and 0.4 M, respectively. Lysine, asparagine, and glutamate accelerated the fibrillation by reducing lag time. <i>N</i>-acetyl-l-glutamic acid induced lag-independent fibrillation, whereas glutamine and asparagine showed concentration-dependent effects on the fibrillation with reduced lag time at higher concentrations. Molecular dynamics simulations revealed that interdomain contacts facilitated the fibrillation. The amino acids interacting predominantly through van der Waals interactions reduced the lag time of α-syn. However, the amino acids having strong electrostatic interactions with the protein disrupted intradomain contacts, favored extended conformation, and inhibited the fibril formation.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-24"},"PeriodicalIF":2.4,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144859179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Shared regulatory factors influencing mRNA translation rate and half-life in yeast.","authors":"Sudipto Basu, Suman Hait, Sudip Kundu","doi":"10.1080/07391102.2025.2540787","DOIUrl":"https://doi.org/10.1080/07391102.2025.2540787","url":null,"abstract":"<p><p>Extensive research has highlighted the role of codon composition in regulating co-translational mRNA decay. Translational efficiency is often measured using a codon usage metric like the codon adaptation index (CAI), while mRNA stability is assessed through sequence- and structure-dependent metrics such as codon stabilization coefficient and internal unstructured segments (IUS). However, the question remains whether sequence-dependent translation parameters can influence mRNA stability, or if stability-related parameters can, in turn, regulate mRNA translation and overall co-translational decay. Our approach integrates yeast mRNA sequence, structural, and ribosomal density (RD) data to explore the interconnected regulatory determinants that govern mRNA translation and degradation. Our findings offer new insights into how codon preferences and mRNA structuredness impact these processes, with CAI predominantly shaping translation rates and IUS affecting mRNA decay. Additionally, we observe that the impact of RD on co-translational mRNA decay is context-specific, depending on the dynamics of the primary regulators. These primary regulators are conserved across the genome and throughout evolution, emphasizing their importance in maintaining cellular function. We propose that optimizing both CAI and IUS is essential for improving mRNA-based drug delivery systems. A deeper understanding of the relationship between these factors could lead to more effective mRNA therapeutics.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-15"},"PeriodicalIF":2.4,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}