Results 71 to 80 of about 6,190 (152)

Artificial intelligence empowers targeted protein degradation: Core technological innovations, multi‐scenario applications, and translational prospects

Smart Molecules, EarlyView.
AI is transforming TPD by improving the design, prediction, and optimization of degraders such as PROTACs, molecular glues, and LYTACs. This review summarizes key AI‐driven advances, highlights applications across drug discovery stages, and discusses remaining challenges and future directions for accelerating the development of therapies against ...
Shuanglin Qin, Rui Peng, Guangshuai Zhang, Si Yan, Jin Xiao, Zishu Liu, Ziyu Tan, Qingqing Xie, Shangjie Li, Wei Luo, Xiaohe Xiao   +10 more
wiley   +1 more source

Towards routine accurate electron‐density studies of biological macromolecules

Acta Crystallographica Section D, EarlyView.
Here, we describe the determination of the highest resolution structure in the PDB at 0.43 Å resolution. Electron‐density maps reveal extensive deformation electron density that is completely accounted for by performing transferable aspherical atom refinements using the DiSCaMB library in BUSTER.We report here the structure of Pyrococcus abyssi ...
Elham Paknia, Claus Flensburg, Michal Leszek Chodkiewicz, Rasmus H. Fogh, Peter Keller, Clemens Vonrhein, Clemens Schulze-Briese, Paulina Maria Dominiak, Gleb Bourenkov, Gérard Bricogne, Ashwin Chari   +10 more
wiley   +1 more source

Thermodynamic characterisation of covalent ligand binding

British Journal of Pharmacology, EarlyView.
Background and Purpose Differential scanning fluorimetry (DSF) is a common and straightforward method to evaluate the thermal stability of proteins and has been heavily used for ligand binding characterisation as well as for screening. One class of compounds that is less typically evaluated by DSF are covalent binders.
Rebecca Hertzman, Maayan Lavie, Almog Nadir, Ronen Gabizon, Nir London   +4 more
wiley   +1 more source

A Single Mutation Increases the Thermostability and Activity of Aspergillus terreus Amine Transaminase

Molecules, 2019
Enhancing the thermostability of (R)-selective amine transaminases (AT-ATA) will expand its application in the asymmetric synthesis of chiral amines.
Wan-Li Zhu, Sheng Hu, Chang-Jiang Lv, Wei-Rui Zhao, Hong-Peng Wang, Jia-Qi Mei, Le-He Mei, Jun Huang   +7 more
doaj   +1 more source

Functional characterization of 42 CK2α de novo variants associated with Okur‐Chung neurodevelopmental syndrome

The FEBS Journal, EarlyView.
Okur‐Chung neurodevelopmental syndrome (OCNDS) is a neurodevelopmental disorder associated with mutations in the gene coding for Protein kinase CK2α. In this work, 42 variants of CK2α associated with OCNDS were characterized in vitro. This included determination of catalytic activity and CK2α/CK2β‐interaction as well as an assessment of evolutionary ...
Alexander Gast, Christian Werner, Karsten Niefind, Joachim Jose   +3 more
wiley   +1 more source

Three Essential Resources to Improve Differential Scanning Fluorimetry (DSF) Experiments [PDF]

, 2020
Abstract Differential Scanning Fluorimetry (DSF) is a method that enables rapid determination of a protein’s apparent melting temperature (Tm a ). Owing to its high throughput, DSF has found widespread application in fields ranging from structural biology to chemical screening.
Wu, Taia, Yu, Joshua, Gale-Day, Zachary, Woo, Amanda, Suresh, Arundhati, Hornsby, Michael, Gestwicki, Jason E.   +6 more
openaire   +1 more source

Blocking protein quality control degradation leads to structural stabilization of DHFR indel variants

The FEBS Journal, EarlyView.
Blocking protein quality control degradation by deleting the E3 ligases Ubr1 or San1 stabilizes many DHFR insertion and deletion variants that are otherwise partially unfolded. These hypomorphic variants regain folding at lower temperatures or upon methotrexate binding, revealing that PQC degradation can remove proteins that are still functionally ...
Sven Larsen‐Ledet, Caroline H. Suhr, Sarah Gersing, Celeste M. Hackney, Amelie Stein, Kaare Teilum, Rasmus Hartmann‐Petersen   +6 more
wiley   +1 more source

Conserved dimerization architecture in C‐type lectins from virus‐vector mosquitoes

The FEBS Journal, EarlyView.
C‐type lectins (CTLs) are involved in the detection of viral/microbial carbohydrates. We studied a family of soluble CTLs in the mosquito Aedes aegypti, which acts as a vector for viruses like dengue and Zika. Using crystallography, biophysics, and structure prediction approaches, we found that these proteins consistently pair together in the same ...
Mattia Bertinelli, Rupesh Balaji Jayachandran, Jack Whitehead, Cédric Leyrat, Annabel v. Clanner, Guido C Paesen, Max Renner   +6 more
wiley   +1 more source

Directional information flow in human frataxin defines allosteric pathways connecting the hydrophobic core to the iron‐binding ridge

The FEBS Journal, EarlyView.
Human frataxin deficiency causes Friedreich's ataxia, yet how iron‐binding events are communicated across the protein is unclear. Using transfer entropy analysis of molecular dynamics simulations, we identify buried hydrophobic core leucines (LEU136, LEU140) as the source of directional signaling toward the iron‐binding acidic ridge.
Kevser Kübra Kırboğa, Ecir Uğur Küçüksille   +1 more
wiley   +1 more source

Click Chemistry-Enabled Parallel Synthesis of N-Acyl Sulfonamides and Their Evaluation as Carbonic Anhydrase Inhibitors

Molecules
A synthetically accessible library of N-acyl sulfonamides was constructed using a combination of copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC) and N-acylation of primary sulfonamides.
Oleksii V. Gavrylenko, Bohdan V. Vashchenko, Vasyl Naumchyk, Bohdan S. Sosunovych, Oleksii Chuk, Oleksii Hrabovskyi, Olga Kuchuk, Alla Pogribna, Sergiy O. Nikitin, Anzhelika I. Konovets, Volodymyr S. Brovarets, Sergey A. Zozulya, Dmytro S. Radchenko, Oleksandr O. Grygorenko, Yurii S. Moroz   +14 more
doaj   +1 more source