Bridging the gap between ribosome structure and biochemistry by mechanistic computations

The wealth of structural and biochemical data now available for protein synthesis on the ribosome presents major new challenges for computational biochemistry. Apart from technical difficulties in modeling ribosome systems, the complexity of the overall translation cycle with a multitude of different kinetic steps presents a formidable problem for computational efforts where we have only seen the beginning. However, a range of methodologies including molecular dynamics simulations, free energy calculations, molecular docking and quantum chemical approaches have already been put to work with promising results. In particular, the combined efforts of structural biology, biochemistry, kinetics and computational modeling can lead towards a quantitative structure-based description of translation.

► Computational modeling and simulation are powerful tools for deriving functional mechanisms from ribosome structures. ► Evaluation of energies is most important for linking structure and function. ► Methods ranging from quantum chemistry to MD simulation can be used to explore the steps of translation. ► Several predictions about ribosome function from computations have been confirmed experimentally. ► Quantitative structure-based descriptions of protein synthesis can be obtained by combining computations with experimental kinetics.