Multiscale Simulations on Biological Energy Catalysis

NAISS 2023/1-31


NAISS 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 NAISS project is a continuation of our 2022 SNIC Large Computing project in which we aim to elucidate molecular principles of proteins that catalyze chemical and light-driven energy transduction in cell respiration and photosynthesis, with highly exciting results from the last funding round. We tackle these principles by integrating state-of-the-art multi-scale simulations that range from hybrid quantum/classical (QM/MM) approaches (DFT and correlated ab initio) to classical atomistic and coarse-grained simulations 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. A new theme in the 2023 project is to address how intrinsic electric fields control proton transfer reactions in proteins. Our work 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 ion pumps and photosynthesis, and 4) enzyme engineering, energy transduction and catalytic principles of molecular chaperones. This computational consortium involves around 20 researchers (one professor, one staff scientist, four post-doctoral fellows, 8 PhD students, 3 master students, and several external collaborators) supported by the ERC, VR, Cancerfonden, the collaborative research center SFB1078 (Berlin), and the KAW foundation.