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.
Dmitry Morozov studied chemistry and received Ph.D. at Moscow State University in Russia (2013). The theses were focused on the development and application of hybrid quantum-mechanics/molecular mechanics (QM/MM) methods for studies of biological systems properties. Since 2013 working in the group of Prof. Groenhof at University of Jyväskylä as a Postdoctoral Researcher. In 2015 received Academy of Finland Postdoctoral Researcher funding. From 2019 he has been working within the BioExcel consortium on the implementation of multiscale methods for performing simulations of chemical and biological systems.
Department of Chemistry and Nanoscience Center, University of Jyväskylä, Finland
Mirko Paulikatstudied chemistry and got his doctoral degree in the field of Computational Chemistry at the University of Goettingen, Germany (2019). In his Ph.D. studies, he investigated spectral properties as well as the mechanisms of thiamin diphosphate dependent enzymes. In 2020, he joined Prof. Carloni’s Computational Biomedicine group at Forschungszentrum Jülich as a postdoctoral researcher. His research focuses on molecular simulations of biologically relevant systems, using high-performance computing QM and QM/MM approaches. From 01/2021, he works within the BioExcel consortium on the application of the therein developed QM/MM interfaces to study proton dynamics of biomolecules in the gas phase.
Institute for Advanced Simulation / Institute of Neuroscience and Medicine, Forschungszentrum Jülich, Germany
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Title: QM/MM Simulation of Fluorescent Proteins and Proton Dynamics