In the realm of drug discovery, a team of researchers from Sorbonne Université, led by Narjes Ansari, Félix Aviat, Jérôme Hénin, Jean-Philip Piquemal, and Louis Lagardère, has developed a novel method to dramatically accelerate the calculation of Relative Binding Free Energy (RBFE). This advancement, published in the Journal of Chemical Theory and Computation, holds significant promise for the energy industry, particularly in the realm of bioenergy and biofuels.
Relative Binding Free Energy calculations are crucial for understanding how different molecules interact with their targets, a process vital for optimizing drug candidates. However, the high computational cost and complexity have limited their widespread use. The researchers introduced a new method called dual-LAO, which builds on the Lambda-ABF-OPES framework. This method combines a dual-topology setup and suitable restraints to significantly speed up the calculation process.
The dual-LAO method, when used with the AMOEBA polarizable force field, achieved an acceleration factor of 15 to 30 times compared to current state-of-the-art methods. This means that calculations that previously took weeks can now be completed in days or even hours. The method also maintains high accuracy and can handle complex molecular changes that were previously challenging, such as scaffold-hopping, buried water displacement, charge changes, ring-opening, and binding pose perturbations.
For the energy sector, this advancement could be particularly useful in the development of biofuels and biocatalysts. Understanding how different molecules interact with enzymes and other biological targets is crucial for optimizing the production of biofuels and other bio-based products. The dual-LAO method could enable researchers to perform these calculations more quickly and accurately, accelerating the development of new and improved bioenergy technologies.
In summary, the dual-LAO method represents a significant leap forward in the field of computational chemistry. Its ability to dramatically accelerate RBFE calculations while maintaining high accuracy and tackling complex molecular changes opens up new possibilities for drug discovery and other fields, including the energy sector. As the researchers continue to refine and improve this method, it is likely to become an invaluable tool for scientists and engineers working to develop the next generation of bioenergy technologies.
Source: Ansari, N., Aviat, F., Hénin, J., Piquemal, J.-P., & Lagardère, L. (2023). Fast, systematic and robust relative binding free energies for simple and complex transformations: dual-LAO. Journal of Chemical Theory and Computation.
This article is based on research available at arXiv.