Developing computational tools to complement experiments in understanding biomolecular function from conformational ensembles

Project Summary/Abstract The mission of the Hamelberg group is to develop computational tools to complement experiments in elucidating the dynamics-function relationship in biomolecules. The group has been continuously making significant contributions to theoretical biochemistry and biophysics, including developing methods for enhanced sampling, free energy calculation, and the analysis of biomolecular dynamic data, and their applications to diverse biological systems. These methods, based on molecular dynamics, can reveal at the atomic level of detail the mechanism of biomolecular function, which is usually difficult to obtain by current experiments. Such detailed knowledge is essential for the understanding and fine-tuning of (patho)physiological processes, which can be leveraged for drug discovery and biomolecular design. The group is dedicated to continuing this endeavor by developing innovative computational tools that are more intimately coupled with experiments, implementing more advanced algorithms able to better identify function-related information from complex data, accompanied by well-established systems for rigorously checking convergence, robustness, and accuracy, and accessible to the broader community of biochemists. These tools will be tested on diverse biological systems of pharmaceutical significance. Our work will help resolve the current challenge that, with the rapid growth of computing power, longer molecular simulations are routinely performed but efficient computational tools to transform the data into knowledge are missing. We envisage that these tools will largely enhance the effectiveness of using molecular simulations to interpret experimental observations and guide new experimental designs by making testable predictions or hypothesis, hence promoting more collaborations between computational and experimental labs that will eventually accelerate new biological discoveries.