Here we analyzed an option to predict the structure of cis-regulatory modules that consist of binding sites of different proteins (heterogeneous cis-regulatory modules) using mutual positional correlations between protein-DNA binding experimental data and computationally identified clusters of binding sites for each of the proteins.
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ACS Nano
January 2025
Department of Chemistry, Emory University, Atlanta, Georgia 30322, United States.
A major challenge in the field of synthetic motors relates to mimicking the precise, motion of biological motor proteins, which mediates processes such as cargo transport, cell locomotion, and cell division. To address this challenge, we developed a system to control the motion of DNA-based synthetic motors using light. DNA motors are composed of a central chassis particle modified with DNA "legs" that hybridize to RNA "fuel", and move upon enzymatic consumption of RNA.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
February 2025
SKKU Advanced Institute of Nanotechnology (SAINT), Sungkyunkwan University, Suwon 16419, Republic of Korea.
The design of organic-peptide hybrids has the potential to combine our vast knowledge of protein design with small molecule engineering to create hybrid structures with complex functions. Here, we describe the computational design of a photoswitchable Ca-binding organic-peptide hybrid. The designed molecule, designated Ca-binding switch (CaBS), combines an EF-hand motif from classical Ca-binding proteins such as calmodulin with a photoswitchable group that can be reversibly isomerized between a spiropyran (SP) and merocyanine (MC) state in response to different wavelengths of light.
View Article and Find Full Text PDFScience
January 2025
Redox and Metalloprotein Research Group, Max Planck Institute of Biophysics, Frankfurt am Main, Germany.
In the ancient microbial Wood-Ljungdahl pathway, carbon dioxide (CO) is fixed in a multistep process that ends with acetyl-coenzyme A (acetyl-CoA) synthesis at the bifunctional carbon monoxide dehydrogenase/acetyl-CoA synthase complex (CODH/ACS). In this work, we present structural snapshots of the CODH/ACS from the gas-converting acetogen , characterizing the molecular choreography of the overall reaction, including electron transfer to the CODH for CO reduction, methyl transfer from the corrinoid iron-sulfur protein (CoFeSP) partner to the ACS active site, and acetyl-CoA production. Unlike CODH, the multidomain ACS undergoes large conformational changes to form an internal connection to the CODH active site, accommodate the CoFeSP for methyl transfer, and protect the reaction intermediates.
View Article and Find Full Text PDFPLoS One
January 2025
Molecular Biophysics Unit, Indian Institute of Science, Bengaluru, Karnataka, India.
PLoS One
January 2025
Laboratory of Analytical and Molecular Chemistry, Faculty of Sciences Ben M'Sik, Hassan II University of Casablanca, Casablanca, Morocco.
Cognitive dysfunction in Alzheimer's disease results from a complex interplay of various pathological processes, including the dysregulation of key enzymes such as acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and monoamine oxidase B (MAO-B). This study proposes and designs a series of novel molecules derived from 8-hydroxyquinoline (Azo-8HQ) as potential multi-target lead candidates for treating AD. An exhaustive in silico analysis was conducted, encompassing docking studies, ADMET analysis, density functional theory (DFT) studies, molecular dynamics simulations, and subsequent MM-GBSA calculations to examine the pharmacological potential of these molecules with the specific targets of interest.
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