“…However, combining the recently introduced multiplicative integral approximation (MIA, [14]), for which the relevant equations are shortly explained in Section 2, with the direct-scF approach [15,16] introduced by Almlof et al [15], a very efficient method is obtained that allows one to study very large systems using ab initio methods. This approach allowed the complete structure optimization using gradient methods of numerous large molecules, among them the steroid, 4,4-dimethylandrostan-3-one [17], the caged hydrocarbon CZ2Hz4 [18], several conformations of the neuroleptic drug Haloperidol, 4-(4-hydroxy-4-p-chlorophenyl-piperidino)4'-fluorobutyrophenone [19], the p-lactamase inhibitor clavulanic acid [20], several dipeptides [21], and, recently, the peptides N-formyl pentaglycine and N-formyl pentaalanine [22].…”