In the first experiment Method 1 (Experiment 1a) and Method 2 (Experiment 1b) from Hess, and a similar implementation from Smina were compared. The number of iterations for Method 2 from the Hess package was chosen to make the number of computations of the gradient of the scoring function in the two packages approximately equal. A separate run was done with reduced grid step (Experiment 1c). This reduction increased the number of nodes in the grid which gives a more accurate approximation of the scoring function. The results of the analysis are presented in Table and Figures . Global optimisation in Method 1 (experiment 1a) is slower than Smina's 1.7 times on average, but for 7074 ligands out of 9500 the resulting score came in better (bigger in absolute value). In experiment 1b (Method 2), Hess is faster than Smina 2.3 times on average, while having 6263 out of 9500 better scores (less than in experiment 1a, but considerably more than half). In experiment 1c (Method 2, finer grid) the numbers are even more in Hess' favor: 3.6 times faster on average, 6792 better scores out of 9500. The results of experiment 1c are shown on Figures and.