Key relationships between the intramolecular H-bond-derived backbone conformation and the bioactivity of the novel fat-accumulation inhibitor (-)-ternatin are examined by analyses of the NMR spectroscopic data and CD spectra of designed analogues. The results reveal that the beta-turn structure of (-)-ternatin is responsible for its potent fat-accumulation inhibitory effect against 3T3-L1 murine adipocytes.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1039/b818903j | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
A Coarse-Grained Simulation Approach for Protein Molecular Conformation Dynamics.
J Phys Chem A
January 2025
Computer Modelling Group, 3710 33 St NW, Calgary, Alberta T2L 2M1, Canada.
Coarse-grained molecular dynamics simulation is widely accepted for assessment of a large complex biological system, but it may also lead to a misleading conclusion. The challenge is to simulate protein structural dynamics (such as folding-unfolding behavior) due to the lack of a necessary backbone flexibility. This study developed a standard coarse-grained model directly from the protein atomic structure and amino acid coarse-grained FF (such as MARTINI FF v2.
View Article and Find Full Text PDFConformationally Restricted Macrocycles as Improved FKBP51 Inhibitors Enabled by Systematic Linker Derivatization.
Angew Chem Int Ed Engl
January 2025
Darmstadt University of Technology: Technische Universitat Darmstadt, Clemens-Schöpf-Institute of Organic Chemistry and Biochemistry, Alarich-Weiss-Strasse 4, 64287, Darmstadt, GERMANY.
Macrocycles are increasingly considered as promising modalities to target challenging intracellular proteins. However, strategies for transitioning from active linear starting points to improved macrocycles are still underdeveloped. Here we explored the derivatization of linkers as an approach for macrocycle optimization.
View Article and Find Full Text PDFMultiple Topology Replica Exchange of Expanded Ensembles for Multidimensional Alchemical Calculations.
J Chem Theory Comput
January 2025
Department of Chemical and Biological Engineering, University of Colorado Boulder, Boulder, Colorado 80309, United States.
Relative free energy (RFE) calculations are now widely used in academia and the industry, but their accuracy is often limited by poor sampling of the complexes' conformational ensemble. To help address conformational sampling problems when simulating many relative binding free energies, we developed a novel method termed multiple topology replica exchange of expanded ensembles (MT-REXEE). This method enables parallel expanded ensemble calculations, facilitating iterative RFE computations while allowing conformational exchange between parallel transformations.
View Article and Find Full Text PDFInvestigation of the impact of R273H and R273C mutations on the DNA binding domain of P53 protein through molecular dynamic simulation.
J Biomol Struct Dyn
February 2025
Laboratory of Integrative Genomics, Department of Integrative Biology, School of Bio Sciences and Technology, Vellore Institute of Technology (VIT), Vellore, India.
The P53 protein, a cancer-associated transcriptional factor and tumor suppressor, houses a Zn ion in its DNA-binding domain (DBD), essential for sequence-specific DNA binding. However, common mutations at position 273, specifically from Arginine to Histidine and Cysteine, lead to a loss of function as a tumor suppressor, also called DNA contact mutations. The mutant (MT) P53 structure cannot stabilize DNA due to inadequate interaction.
View Article and Find Full Text PDFR3Design: deep tertiary structure-based RNA sequence design and beyond.
Brief Bioinform
November 2024
AI Lab, Research Center for Industries of the Future, Westlake University, Zhejiang 310058, China.
The rational design of Ribonucleic acid (RNA) molecules is crucial for advancing therapeutic applications, synthetic biology, and understanding the fundamental principles of life. Traditional RNA design methods have predominantly focused on secondary structure-based sequence design, often neglecting the intricate and essential tertiary interactions. We introduce R3Design, a tertiary structure-based RNA sequence design method that shifts the paradigm to prioritize tertiary structure in the RNA sequence design.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!