IMPORTANCE OF EXPLICIT SALT IONS FOR PROTEIN STABILITY IN MOLECULAR-DYNAMICS SIMULATION

The accurate and efficient treatment of electrostatic interactions is one of the challenging problems of molecular dynamics simulation. Trun cation procedures such as switching or shifting energies or forces lea d to artifacts and significantly reduced accuracy. The particle mesh E wald (PME) method is one approach to overcome these problems by provid ing a computationally efficient means of calculating all long-range el ectrostatic interactions in a periodic simulation box by use of fast F ourier transformation techniques. For the application of the PME metho d to the simulation of a protein with a net charge in aqueous solution , counterions are added to neutralize the system. The usual procedure is to add charge-balancing counterions close to charged residues to ne utralize the protein surface. In the present article, we show that for MD simulation of a small protein of marginal stability, the YAP-WW do main, explicit modeling of 0.2 M ionic strength (in addition to the ch arge-balancing counterions) is necessary to maintain a stable protein structure. Without explicit ions throughout the periodic simulation bo x, the charge-balancing counterions on the protein surface diffuse awa y from the protein, resulting in destruction of the beta-sheet seconda ry structure of the WW domain.