Our illustration of D-galactonate release, selected as the cover art for the April 7 issue of Biophysical Journal, illuminates a wonderful microscopic world hidden to the naked eye. In the image, we can see a D-galactonate molecule narrowly escaping through the intracellular gate of the D-galactonate transporter protein, into the bacterial cytosol. A sugary snack for the bacteria, you might say! Although substrate transport occurs at lightning speed in living organisms, simulating such a process at the atomic level—even with modern computer capabilities—remains daunting. However, with a clever funnel-shaped guide and a “push” from metadynamics-enhanced sampling, we were able to characterize the D-galactonate release process in stunning detail. In particular, we found that something as small as a proton (H+) makes a huge difference in the rate of substrate dissociation. Simulating biological processes at the atomic level is incredibly insightful for addressing scientific questions, and powerful for accelerating progress in medicine and biotechnology.
Our cover image was constructed by using Visual Molecular Dynamics software to depict a snapshot from our simulations and rendered on NVIDIA A30 Tensor Core GPUs hosted by the Advanced Research Computing (ARC) facility at Virginia Tech.
This project was carried out as part of a collaboration fostered through the National Science Foundation–funded International Research Experiences for Students program between Virginia Tech and the Institute of Neuroscience and Medicine, Computational Biomedicine at Forschungszentrum Jülich (FZJ), and in collaboration with the Institute of Biological Information Processing, Molecular and Cellular Physiology at FZJ. The molecular simulations were performed by using high-performance computing resources both at Virginia Tech’s ARC infrastructure and at the Jülich Supercomputing Centre. If you are interested in our research and would like to learn more about the participating groups, please visit https://www.deshmukhgroup.org/, https://www.fz-juelich.de/en/inm/inm-9, https://www.fz-juelich.de/en/ibi/ibi-1.
– Charles Plate, Natalia Dmitrieva, Samira Gholami, Mercedes Alfonso-Prieto, Sanket A. Deshmukh, Davide Mandelli, Paolo Carloni, and Christoph Fahlke