Application of CoLD-CoP to Detecting Competitively and Cooperatively Binding Ligands
NMR utilization in fragment-based drug discovery requires techniques to detect weakly binding fragments and to subsequently identify cooperatively binding fragments. Such cooperatively binding fragments can then be optimized or linked in order to develop viable drug candidates. Similarly, ligands or...
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MDPI AG
2024-09-01
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| Online Access: | https://www.mdpi.com/2218-273X/14/9/1136 |
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| author | Shiva V. Patnala Roberto Robles David A. Snyder |
| author_facet | Shiva V. Patnala Roberto Robles David A. Snyder |
| author_sort | Shiva V. Patnala |
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| description | NMR utilization in fragment-based drug discovery requires techniques to detect weakly binding fragments and to subsequently identify cooperatively binding fragments. Such cooperatively binding fragments can then be optimized or linked in order to develop viable drug candidates. Similarly, ligands or substrates that bind macromolecules (including enzymes) in competition with the endogenous ligand or substrate are valuable probes of macromolecular chemistry and function. The lengthy and costly process of identifying competitive or cooperative binding can be streamlined by coupling computational biochemistry and spectroscopy tools. The Clustering of Ligand Diffusion Coefficient Pairs (CoLD-CoP) method, previously developed by Snyder and co-workers, detects weakly binding ligands by analyzing pairs of diffusion spectra, obtained in the absence and the presence of a protein. We extended the CoLD-CoP method to analyze spectra pairs (each in the presence of a protein) with or without a critical ligand, to detect both competitive and cooperative binding. |
| format | Article |
| id | doaj-art-11f4683ad8694eeeb47c020b4aea6f3f |
| institution | OA Journals |
| issn | 2218-273X |
| language | English |
| publishDate | 2024-09-01 |
| publisher | MDPI AG |
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| series | Biomolecules |
| spelling | doaj-art-11f4683ad8694eeeb47c020b4aea6f3f2025-08-20T01:56:10ZengMDPI AGBiomolecules2218-273X2024-09-01149113610.3390/biom14091136Application of CoLD-CoP to Detecting Competitively and Cooperatively Binding LigandsShiva V. Patnala0Roberto Robles1David A. Snyder2Department of Chemistry, College of Science and Health, William Paterson University, 300 Pompton Road, Wayne, NJ 07470, USADepartment of Chemistry, College of Science and Health, William Paterson University, 300 Pompton Road, Wayne, NJ 07470, USADepartment of Chemistry, College of Science and Health, William Paterson University, 300 Pompton Road, Wayne, NJ 07470, USANMR utilization in fragment-based drug discovery requires techniques to detect weakly binding fragments and to subsequently identify cooperatively binding fragments. Such cooperatively binding fragments can then be optimized or linked in order to develop viable drug candidates. Similarly, ligands or substrates that bind macromolecules (including enzymes) in competition with the endogenous ligand or substrate are valuable probes of macromolecular chemistry and function. The lengthy and costly process of identifying competitive or cooperative binding can be streamlined by coupling computational biochemistry and spectroscopy tools. The Clustering of Ligand Diffusion Coefficient Pairs (CoLD-CoP) method, previously developed by Snyder and co-workers, detects weakly binding ligands by analyzing pairs of diffusion spectra, obtained in the absence and the presence of a protein. We extended the CoLD-CoP method to analyze spectra pairs (each in the presence of a protein) with or without a critical ligand, to detect both competitive and cooperative binding.https://www.mdpi.com/2218-273X/14/9/1136nuclear magnetic resonance (NMR)cooperative/competitive ligand bindingdiffusion spectroscopy (DOSY)fragment-based drug discovery (FBDD) |
| spellingShingle | Shiva V. Patnala Roberto Robles David A. Snyder Application of CoLD-CoP to Detecting Competitively and Cooperatively Binding Ligands Biomolecules nuclear magnetic resonance (NMR) cooperative/competitive ligand binding diffusion spectroscopy (DOSY) fragment-based drug discovery (FBDD) |
| title | Application of CoLD-CoP to Detecting Competitively and Cooperatively Binding Ligands |
| title_full | Application of CoLD-CoP to Detecting Competitively and Cooperatively Binding Ligands |
| title_fullStr | Application of CoLD-CoP to Detecting Competitively and Cooperatively Binding Ligands |
| title_full_unstemmed | Application of CoLD-CoP to Detecting Competitively and Cooperatively Binding Ligands |
| title_short | Application of CoLD-CoP to Detecting Competitively and Cooperatively Binding Ligands |
| title_sort | application of cold cop to detecting competitively and cooperatively binding ligands |
| topic | nuclear magnetic resonance (NMR) cooperative/competitive ligand binding diffusion spectroscopy (DOSY) fragment-based drug discovery (FBDD) |
| url | https://www.mdpi.com/2218-273X/14/9/1136 |
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