POTENTIAL-SCALED MOLECULAR-DYNAMICS AND POTENTIAL ANNEALING - EFFECTIVE CONFORMATIONAL SEARCH TECHNIQUES FOR BIOMOLECULES

An effective conformational search method, potential-scaling molecular dynamics, was described for molecular dynamics (MD) simulations using the explicit solvent water. MD simulations in solution generally yiel d more accurate results than simulations in vacuo, but conformational search methods including the process of raising the temperature (high- temperature MD or simulated annealing) cannot be applied to a system i ncluding a water solvent because these methods affect the whole system and cause unrealistic behavior of water. In the potential-scaled MD, the potential energies involved in the desired degrees of freedom (in our cases, those of solute molecules) are partially scaled down, inste ad of raising the temperature of the whole system. This method was tes ted by using a simple model compound, N-acetylglycyl-N'-methylamide (1 , Figure 1), and proved to be capable of searching the conformational space accurately and more efficiently than the normal MD. Using the id ea of the potential-scaled MD and simulated annealing, we designed a p otential-annealing approach and examined its usefulness. This method c ould find the lowest energy regions in the conformational space of the model system, starting with the different conformers appearing during the potential-scaled MD simulation. It is suggested that the two meth ods described here, potential-scaled MD and potential annealing, have potential as powerful tools in conformational analyses of molecules in aqueous solution, especially in predicting the three-dimensional stru ctures of biomolecules.