Applications of Molecular Dynamics Simulation in Structure Prediction of Peptides and Proteins

Compared with rapid accumulation of protein sequences from high-throughput DNA sequencing, obtaining experimental 3D structures of proteins is still much more difficult, making protein structure prediction (PSP) potentially very useful. Currently, a vast majority of PSP efforts are based on data mining of known sequences, structures and their relationships (informatics-based). However, if closely related template is not available, these methods are usually much less reliable than experiments. They may also be problematic in predicting the structures of naturally occurring or designed peptides. On the other hand, physics-based methods including molecular dynamics (MD) can utilize our understanding of detailed atomic interactions determining biomolecular structures. In this mini-review, we show that all-atom MD can predict structures of cyclic peptides and other peptide foldamers with accuracy similar to experiments. Then, some notable successes in reproducing experimental 3D structures of small proteins through MD simulations (some with replica-exchange) of the folding were summarized. We also describe advancements of MD-based refinement of structure models, and the integration of limited experimental or bioinformatics data into MD-based structure modeling.