Article
Green & Sustainable Science & Technology
Mingna Zheng, Yanwei Li, Rui Xue, Weiliang Dong, Qingzhu Zhang, Wenxing Wang
Summary: Enzymatic depolymerization is an important method for dealing with PET pollution, but the understanding of depolymerization mechanism of environment-relevant PET waste and the influence of PET size on depolymerization efficiency is still limited. This study used nanosized model substrate to investigate the PET depolymerization process and elucidated the effects of PET size and active site features on activation energy barriers. These findings provide important insights for the development of rational enzyme engineering strategies for environmentally friendly and efficient removal of PET.
JOURNAL OF CLEANER PRODUCTION
(2022)
Article
Engineering, Environmental
Mingna Zheng, Yanwei Li, Weiliang Dong, Qingzhu Zhang, Wenxing Wang
Summary: Biotechnology is a promising solution for addressing the global plastic pollution crisis. Understanding the core enzyme mechanisms in the biotransformation process is crucial for enzyme engineering and industrial-scale applications. This study investigated the enantioselectivity of PET hydrolases and identified key structural features that significantly modulate this selectivity. The findings provide important insights for the rational design of enzymes for the recycling of PET plastic waste.
JOURNAL OF HAZARDOUS MATERIALS
(2023)
Article
Chemistry, Applied
Beatriz C. Almeida, Pedro R. Figueiredo, Daniel F. A. R. Dourado, Stephanie Paul, Andreia F. Sousa, Armando J. D. Silvestre, Derek J. Quinn, Thomas S. Moody, Alexandra T. P. Carvalho
Summary: Enzymatic synthesis of polymeric materials is an effective and environmentally friendly method. By characterizing variants of a hyperthermophilic carboxylesterase from Archaeoglobus fulgidus, we can optimize the active site structure and improve the efficiency of polymerization reactions.
ORGANIC PROCESS RESEARCH & DEVELOPMENT
(2022)
Article
Biochemistry & Molecular Biology
Hocheol Lim, Hyeon-Nae Jeon, Seungcheol Lim, Yuil Jang, Taehee Kim, Hyein Cho, Jae-Gu Pan, Kyoung Tai No
Summary: The importance of protein engineering in biopharmaceuticals and biomaterials research and development has increased. Machine learning can reduce experimental effort in protein engineering by identifying optimal sequences that satisfy desired properties. Newly devised protein descriptors showed good performance in diverse datasets, with PCspairs performing the best.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Review
Biotechnology & Applied Microbiology
Zhongdi Song, Qunfeng Zhang, Wenhui Wu, Zhongji Pu, Haoran Yu
Summary: The strategy of rational design is to predict potential mutants based on the understanding of protein structure-function relationships and introduce mutations using site-directed mutagenesis. Rational design methods are universal, fast, and have the potential for quantitative prediction of designed sequence performance. Designing enzymes with improved activity or selectivity is challenging due to the complexity of enzyme structure and limited understanding of structure-function relationships. However, with computational advancement and deeper understanding of enzyme catalysis, rational design can simplify enzyme engineering and its application is increasing.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Lisa Bretschneider, Ingeborg Heuschkel, Katja Buehler, Rohan Karande, Bruno Buehler
Summary: This study successfully constructed a strain of Pseudomonas taiwanensis that efficiently converts cyclohexane to adipic acid, laying the foundation for environmentally friendly production of adipic acid and related polymers.
METABOLIC ENGINEERING
(2022)
Article
Engineering, Environmental
Longgang Jia, Chen Wang, Shujing Zhang, Zhaoting Yuan, Fuping Lu, Yihan Liu
Summary: This study proposed a structure-guided mutation strategy to redesign the tyrosinase into a biocatalyst for producing L-DOPA. The key residues for tyrosinase's function were identified and mutated to create a highly active variant MT6. Quantum mechanics and molecular dynamics simulations revealed that the improved catalytic efficiency was attributed to reduced energy barrier and increased interactions. The orthohydroxylation efficiency of MT6 was tested with L-tyrosine as substrate, demonstrating high conversion rate and productivity.
CHEMICAL ENGINEERING JOURNAL
(2023)
Article
Environmental Sciences
Junhua Zhou, Xin Zhang, Yanwei Li, Shanshan Feng, Qingzhu Zhang, Wenxing Wang
Summary: This study systematically investigates the metabolic activation and transformation mechanism of 2-Nitrofluorene (NF) by cytochrome P450 1A1 (CYP1A1). The results demonstrate that CYP1A1 can activate NF through electrophilic addition and epoxidation reactions, leading to the formation of endocrine-disrupting metabolites. The epoxides produced during the reaction are unstable and can react with hydrated hydrogen ions and hydroxyls, generating 7-hydroxy-2-nitrofluorene, an endocrine disrupter. Additionally, the NF metabolites are found to be more toxic to aquatic organisms and have endocrine-disrupting potential.
ENVIRONMENT INTERNATIONAL
(2022)
Article
Chemistry, Multidisciplinary
Joao T. S. Coimbra, Rui P. P. Neves, Ana Cunha, Maria J. Ramos, Pedro A. Fernandes
Summary: This study investigates the influence of enzyme's dynamical flexibility on reaction mechanisms, using the first step of HIV-1 protease catalyzed reaction as a case study. The results reveal a mechanistic divergence in the enzyme, with two different reaction pathways exhibiting equivalent barriers. An active-site water molecule is suggested to play a role in influencing the mechanistic pathway.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Physics, Multidisciplinary
Manyi Yang, Tarak Karmakar, Michele Parrinello
Summary: The study focuses on the liquid-liquid phase transition of phosphorus, with the determination of a first-order phase transition and the observation of large fluctuations in the vicinity of the second-order critical point.
PHYSICAL REVIEW LETTERS
(2021)
Article
Biochemistry & Molecular Biology
Wei Xia, Yingguo Bai, Pengjun Shi
Summary: By analyzing and designing the active center of Bgl3A, this study found that enhancing hydrophobic interactions and hydrogen-bonding networks can strengthen substrate binding, resulting in four dominant mutants with significantly lower K-m values and higher catalytic efficiencies. These findings may serve as a valuable reference for the design of other beta-glucosidases and glycoside hydrolases.
Article
Environmental Sciences
Zexi Hou, Yanwei Li, Mingna Zheng, Xinning Liu, Qingzhu Zhang, Wenxing Wang
Summary: Recently, the activation mechanism and possible metabolites of heterocyclic PAHs catalyzed by human CYP1A1 have been explored using high level QM/MM calculations. Electrophilic addition was determined as the rate-determining step, followed by possible reactions including epoxidation, NIH shift, and proton shuttle. The main metabolites (hydroxylated carbazoles) were estimated to be more toxic than carbazole.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2023)
Article
Chemistry, Physical
Andrea Rizzi, Paolo Carloni, Michele Parrinello
Summary: The method presented extends the theory of targeted free energy perturbation to accurately calculate free energy differences and surfaces at a quantum mechanical level from a cheaper reference potential. Accelerated convergence is achieved by increasing the overlap between target and reference distributions. The method is validated through numerical evaluations in different systems, demonstrating its effectiveness in avoiding systematic errors.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2021)
Article
Chemistry, Physical
Shiduo Zhang, Wenlong Yang, Minyi Zhang
Summary: This study investigates the reaction mechanism of the unexplored substrate L-Arg derivative L-DHMAd in the critical N-nitrosation reaction catalyzed by the SznF enzyme through the combined quantum mechanics/molecular mechanics method. The optimal N-nitrosation reaction pathway is divided into three reaction steps: superoxo addition with Ce-N omega bond cleavage, O1-O2 bond heterolytic cleavage, and NMe-N omega bond coupling. The rate-determining step is the first reaction step with an energy barrier of 20.6 Kcal/mol. Additionally, the Ce-N omega bond can spontaneously cleave during the first reaction step, contributing to maintaining the Ce sp2 hybridization. Our findings provide insights into the N-nitrosation reaction catalyzed by the SznF enzyme and may inspire further studies in the biomimetic chemistry of SznF enzyme.
CHEMICAL PHYSICS LETTERS
(2023)
Article
Chemistry, Physical
Rui Wang, Xin Tong, Zhihang Long, Ali Imran Charm, Hongyang Zhao, Xin Li, Mengke Cai, Yimin You, Xuping Sun, Zhiming Wang
Summary: Colloidal core/shell quantum dots (QDs) with environmentally friendly features and controllable optoelectronic properties have great potential in emerging solar technologies. In this research, CuInSe (CISe)/ZnSe core/shell QDs were rationally designed and tailored by Mn doping and stoichiometric optimization. The findings indicate that Mn doping in In-rich CISe/ZnSe core/shell QDs can effectively engineer the charge kinetics inside the QDs, enabling efficient charge transfer and reducing recombination. The optimized Mn-doped In-rich CISe/ZnSe core/shell QDs exhibited significantly improved photocurrent density in a solar-driven photoelectrochemical device compared to the pristine CISe/ZnSe core/shell QDs. Transition metal doping in green nonstoichiometric core/shell QDs could provide a new strategy for achieving high-efficiency solar energy conversion applications.
Article
Chemistry, Medicinal
Juliana Castro-Amorim, Ana Oliveira, Ashis K. Mukherjee, Maria J. Ramos, Pedro A. Fernandes
Summary: In this study, the catalytic mechanism of RVV-X was determined using a density functional theory/molecular mechanics approach. The results showed that the catalytic process occurs in two steps, involving nucleophilic attack and protonation of the substrate. Zn2+ was found to play a unique role in catalysis by lowering the pKa of the Zn2+-bound water molecule.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Biochemistry & Molecular Biology
Joao Carneiro, Rita P. Magalhaes, Victor de la Oliva M. Roque, Manuel Simoes, Diogo Pratas, Sergio F. Sousa
Summary: This study developed a machine learning multitechnique consensus workflow to predict the protein targets of molecules with confirmed inhibitory activity against biofilm formation by Pseudomonas aeruginosa. The implemented algorithm is freely available and can be improved as more data become available.
JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN
(2023)
Article
Chemistry, Medicinal
Juliana Castro-Amorim, Ana Novo de Oliveira, Saulo Luis Da Silva, Andreimar M. Soares, Ashis K. Mukherjee, Maria Joao Ramos, Pedro A. . Fernandes
Summary: Snake venom-secreted phospholipase A(2) (svPLA(2)) enzymes play a crucial role in envenoming by disrupting the cell membrane's integrity and inducing various pharmacological effects. However, the reaction mechanisms of svPLA(2) are still not fully understood. This review presents and analyzes the most plausible reaction mechanisms, including the single-water mechanism and the assisted-water mechanism. The importance of interfacial activation and a potential catalytic mechanism for noncatalytic PLA(2)-like proteins are also discussed.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Physical
Jovana B. Araskov, Natalia Maciejewska, Mateusz Olszewski, Aleksandar Visnjevac, Vladimir Blagojevic, Henrique S. Fernandes, Sergio F. Sousa, Adrian Puerta, Jose M. Padron, Berta Barta Hollo, Miguel Monge, Maria Rodriguez-Castillo, Jose M. Lopez-de-Luzuriaga, Ozlem Uguz, Atif Koca, Tamara R. Todorovic, Nenad R. Filipovic
Summary: In this study, three neutral Zn(II) complexes with pyridine-based TH ligands were synthesized and characterized. The influence of the ligands' charge on the structure, intermolecular interactions, and photophysical properties was investigated. The deprotonation of the ligands mainly affected the relative energies of electronic levels in the complexes, resulting in similar photoluminescence mechanisms and quantum yields. The substituents at the ligands' periphery had localized effects on the selected quantum molecular descriptors of the complexes.
JOURNAL OF MOLECULAR STRUCTURE
(2023)
Review
Biochemistry & Molecular Biology
Maria F. Araujo, Elisabete M. S. Castanheira, Sergio F. Sousa
Summary: Insecticides are crucial in controlling the spread of insect-borne diseases and protecting crop health. They are formulated to kill or manage insect populations, but their use can have potential consequences on non-target species, the environment, and human health. It is important to follow recommended instructions and employ integrated pest management practices for responsible and sustainable utilization. This review article provides a comprehensive examination of insecticides, including their modes of action, physiological targets, impacts on the environment and human health, and alternatives.
Article
Biochemistry & Molecular Biology
Joao P. M. De Sousa, Nuno C. S. A. Oliveira, Pedro A. Fernandes
Summary: (S)-Norcoclaurine is a crucial compound for the biosynthesis of benzylisoquinoline alkaloids, including various drugs. The genetic modification of (S)-norcoclaurine synthase has been proven to be an effective strategy for large-scale bioproduction of (S)-norcoclaurine in heterologous hosts such as bacteria or yeast.
Article
Chemistry, Physical
Rui P. P. Neves, Bruno Araujo, Maria J. Ramos, Pedro A. Fernandes
Summary: The bacterium Rhodococcus erythropolis (strain IGTS8) has a significant potential in the industry for its ability to remove sulfur from crude oil through the 4S metabolic pathway. The rate-limiting enzyme DszC is prone to feedback inhibition. Molecular docking and dynamics simulations were used to identify binding sites wherein two products of the pathway induce feedback inhibition. The study revealed four potential binding sites, and the proposed mechanism of feedback inhibition involves disturbance of oligomerization and weakening of key interactions within DszC.
Article
Pharmacology & Pharmacy
Carlos F. M. Silva, Teresa Leao, Filipa Dias, Ana M. Tomas, Diana C. G. A. Pinto, Eduardo F. T. Oliveira, Ana Oliveira, Pedro A. Fernandes, Artur M. S. Silva
Summary: Leishmaniasis is a neglected disease mainly affecting people in developing countries, with approximately 350 million people at risk. The lack of vaccines and chemotherapy has led to an increase in the incidence of the disease. A computational study focusing on a specific enzyme of the parasite has identified potential inhibitors, indicating the promise of using these compounds for developing novel antileishmanial drugs.
Article
Chemistry, Medicinal
Mariana Novo Belchor, Caroline Ramos da Cruz Costa, Airam Roggero, Laila L. F. Moraes, Ricardo Samelo, Isabelly Annunciato, Marcos Antonio de Oliveira, Sergio F. Sousa, Marcos Hikari Toyama
Summary: In this study, in silico tools were used to evaluate the potential of quercetin methylated derivatives in inhibiting snake venom toxins and phospholipase A2. The results showed that certain residues, including Leu2, Phe5, Tyr28, glycine in the calcium-binding loop, His48, and Asp49, were the main targets for inhibition. These findings are important for further research on the anti-inflammatory effects of quercetin derivatives.
Article
Chemistry, Medicinal
Joas T. S. Coimbra, Pedro A. Fernandes, Maria J. Ramos
Summary: Due to antibiotic resistance, it is crucial to explore new antibiotics and/or strategies to counter resistance. This study used molecular dynamics simulations and quantum mechanics/molecular mechanics methods to investigate the degradation of a streptogramin B antibiotic by Vgb lyase and assess the impact of point mutations on the reaction. The findings provide valuable insights into the linearization reactions of cyclic antibiotics and aid in the development of novel strategies against antibiotic resistance.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Microbiology
E. Mauro, D. Lapaillerie, C. Tumiotto, C. Charlier, F. Martins, S. F. Sousa, M. Metifiot, P. Weigel, K. Yamatsugu, M. Kanai, H. Munier-Lehmann, C. Richetta, M. Maisch, J. Dutrieux, J. Batisse, M. Ruff, O. Delelis, P. Lesbats, V. Parissi
Summary: Researchers used AlphaLISA technology to monitor the interaction between retroviral intasomes and nucleosomes, and identified drugs that disrupt or prevent their association, inhibiting HIV-1 integration.
Article
Materials Science, Multidisciplinary
Fabio G. Martins, Chanchal Kiran Thakur, Chandrabose Karthikeyan, N. S. Hari Narayana Moorthy, Sergio F. Sousa
Summary: This study used computational models to investigate the pH dependent loading of doxorubicin onto multiwalled carbon nanotubes (MWCNTs). The results showed that systems under acidic conditions had lower adsorption compared to their neutral counterparts, and carbohydrate-modified lysinated MWCNTs had higher adsorption compared to pristine or carboxylated nanotubes. These findings are consistent with previous experimental work and suggest that sugar-tethered multiwalled carbon nanotubes hold promise for doxorubicin delivery to cancer cells.
Article
Chemistry, Multidisciplinary
Carola Jerves, Rui P. P. Neves, Saulo L. da Silva, Maria J. Ramos, Pedro A. Fernandes
Summary: The PETase enzyme from Ideonella sakaiensis can degrade PET at room temperature. Computational enzyme optimization can accelerate enzyme engineering. Mutations can stabilize transition states and decrease activation barriers. Rational enzyme engineering on PETase and other enzymes is encouraged.
NEW JOURNAL OF CHEMISTRY
(2023)
Article
Chemistry, Physical
Tatiana F. Vieira, Nuno M. F. S. A. Cerqueira, Manuel Simoes, Sergio F. Sousa
Summary: PqsD is an enzyme involved in the synthesis of essential secondary metabolites for Pseudomonas quinolone signal (PQS) inducer molecules. Inhibition of PqsD activity can inhibit biofilm formation and can be combined with PqsR inhibition. This study used computational methods to screen and select eight compounds as potential quorum sensing inhibitors.
MOLECULAR SYSTEMS DESIGN & ENGINEERING
(2024)