Minisymposium Presentation

Most processes of life are the result of polyvalent interactions between macromolecules. Due to their size, the times these interactions require to form and break are often prohibitively long for interrogation using molecular dynamics. Additionally, the heterogeneous composition of biological systems challenges current force fields (FFs). In my talk, I will discuss the difficulties arising from the interplay of statistical (sampling) and modeling (FF) errors, using a protein binding different RNA molecules, including its cognate sequence, as a model system. We investigated the effects of two common biological FFs on the configuration of RNA in water, and I will show that the choice of force field alone can lead to slow conformational relaxation, which also impacts the unbinding of RNA from the protein. I will provide evidence how the enhanced sampling technique PIGS allowed us to quantitatively study this unbinding process. The joint analysis of a data set across different RNA sequences points towards similarly sized contributions from sequence changes adjacent to the central adenine and from methylating the latter, consistent with experimental data. This provides evidence that the combination of PIGS with the FF is able to model equilibrium properties of protein-RNA-complexes on a timescale of hundreds of microseconds.