PCVA worked well for the catechol O-methyltransferase (COMT) compared to the CSA and FSA results of Kulik and co-workers with much lower computational effort for the construction of the QM region. In this work, we want to address whether additional simplifications or variations can be introduced to further decrease computational cost without loss of accuracy. In addition, we will investigate the ability of PCVA to reasonably work for other systems than COMT. For this, we apply the approach to the triosephosphate isomerase (TIM) which has been a subject to CDA in earlier work , and we extend PCVA to the use for a non-protein system, namely a DNA system which has been extensively investigated concerning QM/MM energy convergence by Roßbach and Ochsenfeld .