Article
Chemistry, Applied
Lucile Lecas, Vincent Dugas, Claire Demesmay
Summary: Affinity chromatography, often overlooked in receptor/ligand studies, offers new perspectives with its simplicity and ability to provide diverse information. Different immobilization strategies have been developed to encompass a wide range of applications, from ligand-ranking to fragment screening and identification of active components from natural extracts.
SEPARATION AND PURIFICATION REVIEWS
(2021)
Article
Multidisciplinary Sciences
Trung Hai Nguyen, Van N. T. La, Kyle Burke, David D. L. Minh
Summary: Bayesian regression is used to infer parameters of thermodynamic binding models from isothermal titration calorimetry measurements with enantiomeric mixtures as titrants. The multimodal posterior density indicates the need for additional data with different protocols to uniquely determine the parameters. Models of increasing complexity are compared using model selection criteria, and a variation of bridge sampling is developed to accurately estimate the Bayes factor.
Article
Biochemistry & Molecular Biology
Timothy Q. Vu, Lucas E. Sant'Anna, Neha P. Kamat
Summary: The addition of cell-targeting moieties and polyethylene glycol (PEG) to nanoparticle (NP) drug delivery systems improves the biodistribution, specificity, and uptake of therapeutic cargo. Lipid phase separation in nanoparticles can modulate liposome avidity by changing the proximity of PEG and targeting protein molecules, enhancing the binding of liposomes to cancer cells.
Article
Biochemistry & Molecular Biology
Sebastian Korste, Stephan Settelmeier, Lars Michel, Andrea Odersky, Pia Stock, Fabrice Reyes, Elias Haj-Yehia, Markus S. Anker, Anika Grueneboom, Ulrike B. Hendgen-Cotta, Tienush Rassaf, Matthias Totzeck
Summary: Cancer survival rates have increased due to improvements in therapy regimes and immunomodulatory drugs. Combination therapies of anthracyclines and immune checkpoint inhibitors (ICIs) have been proposed to remove neoplastic cells. However, prior anthracycline exposure may make the heart vulnerable to increased toxicity from subsequent ICI therapy. This study shows that anthracycline treatment affects the PD1/PDL1 signaling pathway in cardiac tissue, potentially increasing susceptibility to immune-related adverse events of anti-PD1/PDL1 cancer therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Bo Cai, Casey J. Krusemark
Summary: A novel assay method combining DNA encoding with split-and-pool sample handling is developed to improve small-molecule binding assays to target proteins. The approach involves affinity labeling of DNA-linked ligands to a protein target, allowing for quantification of DNA barcodes to detect ligand binding. This method demonstrates potential utility in high-throughput small-molecule screening.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Biochemistry & Molecular Biology
Marco van den Noort, Marijn de Boer, Bert Poolman
Summary: This study demonstrates that different ligands induce distinct bound conformations, and by changing the free energies of available conformations, ligand affinity can be adjusted. Experimental data on the maltose-binding protein (MBP) from Escherichia coli reveals that ligand affinity can be modulated through altering conformations.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Chemistry, Analytical
Madeleine Ramona Volz, Bjoern Moosmann
Summary: This article presents the development of a mass-spectrometry-based binding assay for determining the binding affinities of compounds at the human mu-opioid receptor. The assay has a short runtime, high sensitivity, and produces results consistent with radioactive binding assays. It can be used to determine the receptor binding affinities of newly emerging designer opioids.
ANALYTICA CHIMICA ACTA
(2022)
Review
Biochemistry & Molecular Biology
Yuxiao Wang, Qihong Jiao, Jingxuan Wang, Xiaojun Cai, Wei Zhao, Xuefeng Cui
Summary: Predicting the binding affinities between target proteins and small molecule drugs is crucial for drug research and design. Deep learning methods have been widely utilized for precise affinity prediction. This study analyzes and discusses various deep learning methods, and conducts experiments to evaluate their prediction capabilities. By combining the strengths of the four models, improvements in prediction accuracy are achieved.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Article
Chemistry, Medicinal
Andrew T. McNutt, David Ryan Koes
Summary: In this study, a Siamese convolutional neural network (CNN) is proposed for the prediction of relative binding free energy (RBFE) between two bound ligands. The network shows improved performance in RBFE prediction compared to a standard CNN, and its predictive performance varies among different protein families. Additionally, the RBFE prediction performance can be enhanced through few-shot learning during model training.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Biochemistry & Molecular Biology
Maria Joao Moreno, Armindo Salvador
Summary: Ligand-protein interactions in complex media with lipids can influence the apparent affinity and should be considered when studying protein interactions. This study presents a framework to quantitatively characterize these interactions and explores the validity of commonly used approximations. The results show that ligand lipophilicity and lipid bilayer volume impact the apparent ligand-protein affinity, with exceptions for very polar ligands and ligands with supralinear increase in affinity with lipophilicity. The study also discusses important parameters for exploring the specificity of membrane proteins.
Article
Biochemistry & Molecular Biology
Huimin Shen, Youzhi Zhang, Chunhou Zheng, Bing Wang, Peng Chen
Summary: This paper proposes a new cascade graph-based convolutional neural network architecture for accurately predicting the binding affinity between proteins and ligands. The method deals with non-Euclidean irregular data and outperforms most current methods in experiments, showing superior performance in predicting protein-ligand binding affinity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Medicinal
Changchang Liu, Peter Kutchukian, Nhan D. Nguyen, Mohammed AlQuraishi, Peter K. Sorger
Summary: This study presents a computational approach for qualitative and quantitative kinome-wide binding measurements using structure-based machine learning. The approach outperforms methods trained on crystal structures alone and structure-free methods in predicting kinase-compound interaction affinities. It also successfully captures known kinase biochemistry and generalizes well to distant kinase sequences and compound scaffolds.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Chemistry, Medicinal
Xiaoyang Qu, Lina Dong, Jinyan Zhang, Yubing Si, Binju Wang
Summary: This study incorporates the features extracted from protein-bound waters into machine learning-based scoring functions using the HydraMap method. The results show that this approach consistently improves the performance of the scoring functions, including their scoring, ranking, and docking power.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Chemistry, Medicinal
Yishui Li, Runduo Liu, Jie Liu, Haibin Luo, Chengkun Wu, Zhe Li
Summary: This paper presents a newly implemented open source graph-based weighted cycle closure algorithm, which improves the calculation accuracy by considering different error contributions from different paths. The program also provides a new path-independent molecular error calculation method.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Chemistry, Medicinal
Xiaochen Bo, Song He, Shengqi Wang, Qingyu Li, Xiaochang Zhang, Lianlian Wu
Summary: In this study, a novel model named PLAMoRe was proposed to predict protein-ligand binding affinity. The model represents compounds based on both structural and bioactive properties and contains three feature extractors. Experimental results demonstrate the competitiveness and reliability of PLA-MoRe.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Editorial Material
Biochemical Research Methods
Agnes Szabo, Peter Nagy
Article
Pharmacology & Pharmacy
Gyula Batta, Levente Karpati, Gabriela Fulaneto Henrique, Gabriella Toth, Szabolcs Tarapcsak, Tamas Kovacs, Florina Zakany, Istvan M. Mandity, Peter Nagy
Summary: Cell penetrating peptides can be affected by the biophysical properties of the cell membrane. Treatment with atorvastatin can significantly increase the endosomal escape of penetratin.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Oncology
Tamas Kovacs, Florina Zakany, Peter Nagy
Summary: This paper provides a concise overview of how receptor tyrosine kinases are activated and their association with cancer. Understanding the regulation of cell fate and motility can potentially lead to advancements in cancer treatment. The role of lipid-protein interactions in receptor activation is also discussed.
Article
Biochemistry & Molecular Biology
Laszlo Imre, Erfaneh Firouzi Niaki, Rosevalentine Bosire, Peter Nanasi, Peter Nagy, Zsolt Bacso, Nubar Hamidova, Yves Pommier, Albert Jordan, Gabor Szabo
Summary: This study explores the roles and interactions of polyamines (PAs) in the nucleus, specifically their effect on nucleosome stability. The results demonstrate that PAs, such as spermine, spermidine, and putrescine, have a strong destabilizing effect on nucleosomes in the millimolar concentration range. This effect is dependent on pH and salt concentration, and remains significant even at neutral pH. It was also found that PA treatment does not affect the integrity of genomic DNA. Furthermore, the study shows that PAs bind to DNA, as evidenced by the displacement of ethidium bromide.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2022)
Article
Engineering, Biomedical
Zoltan Csernatony, Sandor Mano, Zsolt Tiba, Geza Husi, Zoltan Jonas, Timea Varadi, Lorand Csamer, Agnes Eva Kovacs
Summary: This study aims to find an industrial lubricant that is most similar to biologically lubricating fluids in order to standardize the results of in vitro mechanical tests and prevent biological hazards.
EXPERT REVIEW OF MEDICAL DEVICES
(2022)
Article
Pharmacology & Pharmacy
Mo'ath Yousef, Ildiko Szabo, Jozsef Muranyi, Francoise Illien, Dora Soltesz, Csaba Bato, Gabriella Toth, Gyula Batta, Peter Nagy, Sandrine Sagan, Zoltan Banoczi
Summary: This study demonstrates the preparation and investigation of efficient cell-penetrating peptides (CPPs) and explores the possibility of using unnatural aromatic amino acids to mimic the properties of tryptophan. These highly active CPPs have been successful in delivering antitumor drugs into specific cell lines.
Review
Pharmacology & Pharmacy
Tamas Kovacs, Peter Nagy, Gyorgy Panyi, Lajos Szente, Zoltan Varga, Florina Zakany
Summary: Cyclodextrins are a versatile family of cyclic oligosaccharides that can form non-covalent host-guest inclusion complexes in pharmaceutical formulations. They have extensive applications in the pharmaceutical field due to their ability to enhance the solubility, stability, and bioavailability of drug molecules. Despite being considered inert carriers, cyclodextrins can interact not only with small molecules but also with lipids and proteins, influencing protein function indirectly through alterations in biophysical properties and lateral heterogeneity of bilayers. These interactions have great potential in therapy but have not been fully explored yet.
Article
Biochemical Research Methods
Agnes Batta, Timea Hajdu, Peter Nagy
Summary: Forster resonance energy transfer (FRET) is a radiationless interaction used to study protein oligomerization and structure with distance dependence. This study presents a method that improves FRET measurement precision by using microbeads with a calibrated number of antibody binding sites and a donor-acceptor mixture. The proposed method demonstrates superior reproducibility compared to the conventional approach and can be widely applied for the quantification of FRET experiments in biological research.
Article
Physiology
Tibor G. Szanto, Ferenc Papp, Florina Zakany, Zoltan Varga, Carol Deutsch, Gyorgy Panyi
Summary: Szanto et al. provide evidence supporting the communication between the activation gate and the inactivation gate in K-V channels through the rearrangement of S6, including its rotation. By engineering cysteines at specific S6 positions and testing their accessibility to cysteine-modifying reagents, the researchers found that the coupling between the gates is mediated by rearrangements in the S6 segment. These rearrangements involve a rigid rotation of S6 and concomitant changes in its environment during slow inactivation of Shaker K-V channels.
JOURNAL OF GENERAL PHYSIOLOGY
(2023)
Review
Cell Biology
Florina Zakany, Istvan M. Mandity, Zoltan Varga, Gyorgy Panyi, Peter Nagy, Tamas Kovacs
Summary: Every cell textbook states that the primary function of the plasma membrane is to separate cells and control the intracellular space. While most hydrophilic molecules larger than 1 kDa cannot permeate the hydrophobic cell membrane, cell-penetrating peptides (CPPs) can do so without compromising membrane integrity. Coupling biologically relevant cargos to CPPs shows promise in delivering membrane-impermeable drugs into specific cell types. This review aims to outline the membrane penetration pathways of CPPs and examine how membrane properties influence their uptake mechanisms.