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学者姓名：洪晓昆
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Abstract ：
Excited-ground-state transition and strand slippage of RNA play key roles in transcription and translation of central dogma. Due to limitation of current experimental techniques, the dynamic structure ensembles of RNA remain inadequately understood. Molecular dynamics simulations offer a promising complementary approach, whose accuracy depends on the force field. Here, we develop the new version of RNA base-specific force field (BSFF2) to address underestimation of base pairing stability and artificial backbone conformations. Extensive evaluations on typical RNA systems have comprehensively confirmed the accuracy of BSFF2. Furthermore, BSFF2 demonstrates exceptional efficiency in de novo folding of tetraloops and reproducing base pair reshuffling transition between RNA excited and ground states. Then, we explored the RNA strand slippage mechanism with BSFF2. We conducted a comprehensive three-dimensional structural investigation into the strand slippage of the most complex r(G4C2)9 repeat element and presented the molecular details in the dynamic transition along with the underlying mechanism. Our results of capturing the strand slippage, excited-ground transition, de novo folding, and simulations for various typical RNA motifs indicate that BSFF2 should be one of valuable tools for dynamic conformation research and structure prediction of RNA, and a future contribution to RNA-targeted drug design as well as RNA therapy development. © 2024 American Chemical Society.
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| GB/T 7714 | Li, Z. , Song, G. , Zhu, J. et al. Excited-Ground-State Transition of the RNA Strand Slippage Mechanism Captured by the Base-Specific Force Field [J]. | Journal of Chemical Theory and Computation , 2024 , 20 (14) : 6082-6097 . |
| MLA | Li, Z. et al. "Excited-Ground-State Transition of the RNA Strand Slippage Mechanism Captured by the Base-Specific Force Field" . | Journal of Chemical Theory and Computation 20 . 14 (2024) : 6082-6097 . |
| APA | Li, Z. , Song, G. , Zhu, J. , Mu, J. , Sun, Y. , Hong, X. et al. Excited-Ground-State Transition of the RNA Strand Slippage Mechanism Captured by the Base-Specific Force Field . | Journal of Chemical Theory and Computation , 2024 , 20 (14) , 6082-6097 . |
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Intrinsically disordered proteins (IDPs) lack stable tertiary structures under physiological conditions, yet play key roles in biological processes and associated with human complex diseases. Their conformational characteristics and high content of charged residues make the use of polarizable force fields an advantageous for simulating IDPs. The Drude2019IDP polarizable force field, previously introduced, has demonstrated comprehensive enhancements and improvements in dipeptides, short peptides, and IDPs, achieving a balanced sampling between IDPs and structured proteins. However, the performance in simulating 5 dipeptides was found to be underestimate. Therefore, we individually performed reweighting and grid-based energy correction map (CMAP) optimization for these 5 dipeptides, resulting in the enhanced Drude2019IDPC force field. The performance of Drude2019IDPC was evaluated with 5 dipeptides, 5 disordered short peptides, and a representative IDP. The results demonstrated a marked improvement comparing with original Drude2019IDP. To further substantiate the capabilities of Drude2019IDPC, MD simulation and Markov state model (MSM) were applied to wild type and mutant for insulin, to elucidate the difference of conformational characteristics and transition path. The findings reveal that mutation can maintain the monomorphic characteristics, providing insights for engineered insulin development. These results indicate that Drude2019IDPC could be used to reveal the structure-function relationship for other proteins. © 2024
Keyword ：
Conformations Conformations Markov processes Markov processes Structural optimization Structural optimization
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| GB/T 7714 | Cui, Xiaochen , Zheng, Zhuoqi , Rahman, Mueed Ur et al. Drude2019IDPC polarizable force field reveals structure-function relationship of insulin [J]. | International Journal of Biological Macromolecules , 2024 , 280 . |
| MLA | Cui, Xiaochen et al. "Drude2019IDPC polarizable force field reveals structure-function relationship of insulin" . | International Journal of Biological Macromolecules 280 (2024) . |
| APA | Cui, Xiaochen , Zheng, Zhuoqi , Rahman, Mueed Ur , Hong, Xiaokun , Ji, Xiaoyue , Li, Zhengxin et al. Drude2019IDPC polarizable force field reveals structure-function relationship of insulin . | International Journal of Biological Macromolecules , 2024 , 280 . |
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The synthesis of steroids is challenging through multistep steroidal core modifications with high site-selectivity and productivity. In this work, a novel enzymatic cascade system was constructed for synthesis of testolactone by specific C17 lactonization/Δ1-dehydrogenation from inexpensive androstenedione using an engineered polycyclic ketone monooxygenase (PockeMO) and an appropriate 3-ketosteroid-Δ1-dehydrogenase (ReKstD). The focused saturation mutagenesis in the substrate binding pocket was implemented for evolution of PockeMO to eliminate the bottleneck effect. A best mutant MU3 (I225L/L226V/L532Y) was obtained with 20-fold higher specific activity compared to PockeMO. The catalytic efficiency (kcat/Km) of MU3 was 171-fold higher and the substrate scope shifted to polycyclic ketones. Molecular dynamic simulations suggested that the activity was improved by stabilization of the pre-lactonization state and generation of productive orientation of 4-AD mediated by distal L532Y mutation. Based on that, the three genes, MU3, ReKstD and a ketoreductase for NADPH regeneration, were rationally integrated in one cell via expression fine-tuning to form the efficient single cell catalyst E. coli S9. The single whole-cell biocatalytic process was scaled up and could generate 9.0 g/L testolactone with the high space time yield of 1 g/L/h without steroidal by-product, indicating the potential for site-specific and one-pot synthesis of steroid. © 2024
Keyword ：
Biosynthesis Biosynthesis Cell engineering Cell engineering Cytology Cytology Escherichia coli Escherichia coli Gene expression Gene expression Ketones Ketones Molecular dynamics Molecular dynamics Molecular orientation Molecular orientation
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| GB/T 7714 | Xu, Xinqi , Zhong, Jinchang , Su, Bingmei et al. Single-cell enzymatic cascade synthesis of testolactone enabled by engineering of polycyclic ketone monooxygenase and multi-gene expression fine-tuning [J]. | International Journal of Biological Macromolecules , 2024 , 275 . |
| MLA | Xu, Xinqi et al. "Single-cell enzymatic cascade synthesis of testolactone enabled by engineering of polycyclic ketone monooxygenase and multi-gene expression fine-tuning" . | International Journal of Biological Macromolecules 275 (2024) . |
| APA | Xu, Xinqi , Zhong, Jinchang , Su, Bingmei , Xu, Lian , Hong, Xiaokun , Lin, Juan . Single-cell enzymatic cascade synthesis of testolactone enabled by engineering of polycyclic ketone monooxygenase and multi-gene expression fine-tuning . | International Journal of Biological Macromolecules , 2024 , 275 . |
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Monascus sp. is an important food microbial resource with the production of cholesterol-lowering agent lovastatin and other healthy metabolites. However, the mycotoxin citrinin naturally produced by Monascus sp. and the insufficient productivity of lovastatin limit its large-scale use in food industry. The aim of this paper is to modify a lovastatin-producing strain Monascus pilosus GN-01 through metabolic engineering to obtain a citrinin-free M. pilosus strain with higher yield of lovastatin. The citrinin synthesis regulator gene ctnR was firstly disrupted to obtain GN-02 without citrinin production. Based on that, the lovastatin biosynthesis genes (mokC, mokD, mokE, mokF, mokH, mokI, and LaeA) were, respectively, overexpressed, and pigment-regulatory gene (pigR) was knocked out to improve lovastatin production. The results indicated ctnR inactivation effectively disrupted the citrinin release by M. pilosus GN-01. The overexpression of lovastatin biosynthesis genes and pigR knockout could lead higher contents of lovastatin, of which pigR knockout strain achieved 76.60% increase in the yield of lovastatin compared to GN-02. These studies suggest that such multiplex metabolic pathway engineering in M. pilosus GN-01 is promising for high lovastatin production by a safe strain for application in Monascus-related food.
Keyword ：
Gene knockout Gene knockout Gene overexpression Gene overexpression Lovastatin Lovastatin Monascus pilosus Monascus pilosus
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| GB/T 7714 | Hong, Xiaokun , Guo, Tianlong , Xu, Xinqi et al. Multiplex metabolic pathway engineering of Monascus pilosus enhances lovastatin production [J]. | APPLIED MICROBIOLOGY AND BIOTECHNOLOGY , 2023 , 107 (21) : 6541-6552 . |
| MLA | Hong, Xiaokun et al. "Multiplex metabolic pathway engineering of Monascus pilosus enhances lovastatin production" . | APPLIED MICROBIOLOGY AND BIOTECHNOLOGY 107 . 21 (2023) : 6541-6552 . |
| APA | Hong, Xiaokun , Guo, Tianlong , Xu, Xinqi , Lin, Juan . Multiplex metabolic pathway engineering of Monascus pilosus enhances lovastatin production . | APPLIED MICROBIOLOGY AND BIOTECHNOLOGY , 2023 , 107 (21) , 6541-6552 . |
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Bovine lactoferrin peptide (LFcinB), as an antimicrobial peptide, is expected to be an alternative of antibiotics owing to its broad-spectrum antimicrobial activity and specific mechanism. However, the weak antimicrobial activity, high hemolysis, and poor stability of LFcinB limited its applications in the field of biomedicine, food and agriculture. In order to improve the antimicrobial activity of LFcinB, five mutants were designed rationally, of which mutant LF4 (M10W/P16R/A24L) showed highest antimicrobial activity. The bioinformatics analysis indicated that the improved antimicrobial activity of LF4 was related to its increased cations, higher amphiphilicity and the extension of the & beta;-sheet in the structure. These studies will highlight the important role of bioinformatic tools in designing ideal biopeptides and lay a foundation for further development of antimicrobial peptides.
Keyword ：
Actimicrobial activity Actimicrobial activity Bioinformatics analysis Bioinformatics analysis Bovine lactoferrin peptide Bovine lactoferrin peptide Rational design Rational design
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| GB/T 7714 | Hong, Xiaokun , Liu, Xueqian , Su, Bingmei et al. Improved Antimicrobial Activity of Bovine Lactoferrin Peptide (LFcinB) Based on Rational Design [J]. | PROTEIN JOURNAL , 2023 , 42 (6) : 633-644 . |
| MLA | Hong, Xiaokun et al. "Improved Antimicrobial Activity of Bovine Lactoferrin Peptide (LFcinB) Based on Rational Design" . | PROTEIN JOURNAL 42 . 6 (2023) : 633-644 . |
| APA | Hong, Xiaokun , Liu, Xueqian , Su, Bingmei , Lin, Juan . Improved Antimicrobial Activity of Bovine Lactoferrin Peptide (LFcinB) Based on Rational Design . | PROTEIN JOURNAL , 2023 , 42 (6) , 633-644 . |
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利用生物信息学软件和数据库对从Microbulbifer sp.BN中得到的琼胶酶rAgaN3全长基因进行预测分析,结果表明:重组琼胶酶 rAgaN3理论分子量为31.243 kDa,理论等电为4.81,不稳定系数为26.23,脂肪系数为62.35,平均疏水性系数为-0.662,无跨膜结构域,无信号肽;二级结构表明该蛋白无螺旋结构,有15个折叠结构,其余均为卷曲结构;序列相似性分析表明,蛋白rAgaN3属于糖苷水解酶GH16家族,为β-琼胶酶;以同源蛋白3wz1A(同源性88%)为模板,通过同源建模构建出了蛋白三级结构,并用拉式图进行了结构检验.琼胶酶rAgaN3基因的生物信息学分析,为琼胶酶的异源表达提供了指导,为琼胶酶的定点突变、深入研究其结构和功能的关系打下良好基础.
Keyword ：
基因分析 基因分析 琼胶酶 琼胶酶 生物信息学 生物信息学 蛋白结构 蛋白结构
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| GB/T 7714 | 谢勇 , 洪晓昆 , 鄢仁祥 et al. 重组琼胶酶rAgaN3基因的生物信息学分析 [J]. | 生物信息学 , 2017 , 15 (1) : 16-26 . |
| MLA | 谢勇 et al. "重组琼胶酶rAgaN3基因的生物信息学分析" . | 生物信息学 15 . 1 (2017) : 16-26 . |
| APA | 谢勇 , 洪晓昆 , 鄢仁祥 , 林娟 . 重组琼胶酶rAgaN3基因的生物信息学分析 . | 生物信息学 , 2017 , 15 (1) , 16-26 . |
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