Multiscale Simulations on Biological Energy Catalysis

SNIC 2022/1-29


SNIC Large Compute

Principal Investigator:

Ville Kaila


Stockholms universitet

Start Date:


End Date:


Primary Classification:

10602: Biochemistry and Molecular Biology

Secondary Classification:

10603: Biophysics

Tertiary Classification:

10407: Theoretical Chemistry



The molecular basis of life is established by a complex membrane-bound protein machinery that efficiently captures and converts chemical and light energy and transduces this into other energy forms. This project is a continuation of our 2021 SNIC Large Computing project that aims to elucidate molecular principles of proteins that catalyze chemical and light-driven energy transduction in cell respiration and photosynthesis, with highly exciting results from our last funding round. We tackle these principles by integrating state-of-the-art multi-scale simulations that range from classical atomistic and coarse-grained simulations to hybrid quantum/classical (QM/MM) approaches (DFT and correlated ab initio) to obtain a detailed understanding of the structure, energetics, and dynamics of these proteins on a broad range of timescales and spatial resolutions. The molecular simulations are further integrated with and validated by biochemical, biophysical, and structural experiments. The project aims to link the molecular structure and dynamics with the biological function and, based on these, derive a molecular understanding of how enzymes generate electrochemical energy gradients across biological membranes. Our project focuses on 1) mechanisms of long-range redox-coupled proton/ion-transport in the Complex I superfamily; 2) the functional role of membrane-bound supercomplexes; 3) the functional dynamics of light-driven energy conversion in photosynthesis, and 4) enzyme engineering, energy transduction and catalytic principles of molecular chaperones. This computational consortium involves around 20 researchers (one professor, three staff scientists, five post-doctoral fellows, 8 PhD students, 1 master student, 2 visitors) supported by the ERC, VR, Cancerfonden, and the KAW foundation.