ON ACHIEVING BETTER THAN 1-ANGSTROM ACCURACY IN A SIMULATION OF A LARGE PROTEIN - STREPTOMYCES-GRISEUS PROTEASE-A

Computational methods are frequently used to simulate the properties o f proteins. In these studies accuracy is clearly important, and the im provement of accuracy of protein simulation methodology is one of the major challenges in the application of theoretical methods, such as mo lecular dynamics, to structural studies of biological molecules. Much effort is being devoted to such improvements. Here, we present an anal ysis of a 187-ps molecular dynamics simulation of the serine protease Streptomyces griseus protease A in its crystal environment. The reprod uction of the experimental structure is considerably better than has b een achieved in earlier simulations-the root mean square deviation of the simulated structure from the x-ray structure being less than 1 ang strom, a significant step toward the goal of simulating proteins to wi thin experimental error. The use of a longer cutoff with truncation ra ther than a switching function, inclusion of all crystalline water and the counterions in the crystallization medium, and use of the consist ent valence force field characterize the differences in this calculati on.