Artificial Intelligence Decoding Mysteries of Protein Involved in Diabetes Regulation at Dasman Institute
The Dasman Diabetes Institute, funded by the Kuwait Foundation for the Advancement of Sciences (KFAS), has made a significant breakthrough in the understanding of type 2 diabetes (T2D) research. The team, led by Dr. Anwar Mohammed, has published a new study in the Journal of Cellular and Molecular Medicine, revealing how the transcription factor KLF15 interacts with DNA at the atomic level.
The research approach used by the team combines molecular modeling, dynamic simulation, and energy analysis. The study, which is supported by the KFAS, used the AlphaFold 3.0 platform, an artificial intelligence tool, to accurately predict the 3D structure of the interaction between the KLF15 protein and a key genetic element.
KLF15 binds DNA through zinc finger domains at atomic detail, a fact that has been structurally modeled for the first time using AlphaFold 3.0. This transcription factor plays a crucial regulatory role in glucose metabolism and gluconeogenesis, forming complexes on promoters of metabolic genes, such as Srebf1, to modulate pathways relevant to glucose and lipid homeostasis.
The findings of the study reflect Kuwait's commitment to precision medicine and the application of artificial intelligence in addressing chronic diseases like diabetes. The study also underscores Kuwait's growing role in the global biomedical research landscape.
The team identified four critical sites on the KLF15 protein as potential starting points for novel drug development. By targeting the precise atomic interactions between KLF15 and DNA, it is possible to design highly specific small molecules or peptides that modulate KLF15 activity, either enhancing or inhibiting its DNA binding in a controlled manner. Such molecules could fine-tune the expression of metabolic genes, offering a novel therapeutic strategy for managing glucose levels in T2D.
This integrated computational approach accelerates the drug discovery cycle, reduces reliance on difficult and costly crystallography experiments, and provides atomic-level insights necessary to develop next-generation allosteric modulators or transcription factor inhibitors tailored for complex diseases like T2D.
The use of AlphaFold 3.0 facilitates this process by predicting accurate 3D structures of KLF15 and its complexes, which can be integrated into computational drug discovery pipelines including virtual screening of compound libraries targeting the KLF15 DNA-binding domain interface, rational design of molecules disrupting or stabilizing KLF15-DNA contacts, and simulating molecular dynamics to assess binding stability and efficacy.
Dr. Anwar Mohammed states that the study marks a significant step towards understanding KLF15's role in regulating glucose metabolism. The findings were reported by Al-Jarida daily. This research holds promise for developing innovative precision therapeutics for type 2 diabetes management.
- The significant breakthrough in type 2 diabetes research by The Dasman Diabetes Institute, funded by the Kuwait Foundation for the Advancement of Sciences (KFAS), utilizes artificial intelligence (AI) through the AlphaFold 3.0 platform to model the atomic-level interaction between KLF15, a transcription factor, and DNA, contributing to the understanding of KLF15's role in regulating glucose metabolism.
- The team's findings in medical-conditions like type 2 diabetes (T2D) reveal the crucial role of KLF15 in glucose metabolism and gluconeogenesis, and they have identified four critical sites on the KLF15 protein as potential starting points for the development of novel drugs to manage T2D.
- The integrated computational approach employed by the team, combining molecular modeling, dynamic simulation, and energy analysis, accelerates the discovery of next-generation allosteric modulators or transcription factor inhibitors tailored for complex diseases like T2D, leveraging AI technology to design highly specific small molecules or peptides that modulate KLF15 activity for precision therapeutics in T2D management.
