BioExcel Webinar #65: QM/MM Simulation of Fluorescent Proteins and Proton Dynamics

This webinar presents two examples of research done within BioExcel that demonstrates how hybrid quantum/classical (QM/MM) simulations using GROMACS, CP2K and CPMD performed on high-performance computing (HPC) resources can be used to elucidate biomolecular properties and mechanisms not accessible through a purely classical description. As well as giving insight into particular systems of interest – fluorescent proteins and proton dynamics in bioanalytical mass spectrometry – the webinar serves as an illustration of how the QM/MM approach generally and the above software in particular can be used productively to tackle biomolecular problems. Fluorescent proteins are the backbone for high-resolution biological imaging, but designing suitable proteins for specific experimental conditions is difficult. The goal of our work in BioExcel is to unlock the predictive power of MD and QM/MM simulations for predicting and optimizing the properties of such systems. We have thus developed a protocol to automatically compute the relevant quantities of these proteins and their mutants based on established atomistic simulation methods. The protocol combines (i) force field MD simulations with GROMACS, (ii) PMX and free-energy calculations, and (iii) QM/MM calculations to predict the thermostability (protein folding and oligomerization affinity) and photochemical properties (absorption spectrum and emission spectrum) of fluorescent proteins. Mass spectrometry has become a powerful tool in bioanalytics and can predict structural data of biomolecules at low resolution. Indeed, mass spectrometry requires far less samples than any other higher solution structural biology technique. However, the interpretation of the data is non-trivial. Beside structural changes upon passage from solution into the gas phase, one of the main difficulties in interpreting the data is the presence of quantum phenomena associated with proton transfer. Atomistic simulation gives invaluable insights on these processes. Here, we studied such phenomena by the application of high-performance computing QM/MM software developed within BioExcel to provide important information for the interpretation of mass spectrometry data