Protamine, an arginine-rich basic protein, compacts DNAs in sperm nuclei to densities higher than those in somatic cells. The mechanism of this compaction in sperm cells is even less clear than in somatic cells. Even the preferred binding site, if any, of protamine on DNA is not clearly identified. In this work, we carry out fully atomistic (or all-atom) molecular dynamics simulations to estimate the relative stabilities of protamine binding sites on DNA. Free energy calculated with umbrella sampling on a short arginine stretch bound to the major and minor grooves suggests that a short arginine stretch would prefer the DNA major groove as its binding site. Complementary umbrella sampling simulations where an arginine stretch or a whole protamine is transferred from the major to the minor groove also lead to the same conclusion. We find that the protamine located in the major groove better utilizes the DNA backbone as the binding site and represents the best compromise between enthalpy and entropy gain.
Multiscale molecular modeling (quantum mechanics calculation; molecular dynamics simulation) : Supercomputer-assisted molecular-level understanding of materials and their chemistry; which leads to rational design of high-performance organic-inorganic-hybrid materials for clean and renewable energy as well as low-energy-consumption electronic devices