It is well-known that the results of MD simulations can strongly depend strongly on the accuracy of the applied protein-water force-fields, which may lead to large discrepancies with various experimental measurements . Examples have been observed with state-of-the-art Amber force-fields a99SB*-ILDN with TIP3P , the requirement of fourpoint water model significantly increases computational costs; the force-field is also reported to be too soluble for studying aggregations of some disordered proteins .