“…In this study, in silico experiments were carried out in the catalytic site of the enzyme for estimating the validity regarding the competitive inhibition hypothesis in direct comparison with the SAR notions derived via in vitro screening and, further, for evaluating the contribution of each of the chemical functionalities present in 1 in CBS binding. For enhancing sampling accuracy, induced-fit flexible protein docking (IFD, Schrödinger LLC, New York, NY, USA, 2020) was applied on top-ranked binding geometries determined by rigid docking (Glide, Schrödinger LLC, New York, NY, USA, 2020) [ 55 , 56 , 57 , 58 ]. Overall, docking calculations showed that the dominant binding geometry of 1 would agree, yet not unambiguously, with the scenario that charge-assisted interactions are not necessary for efficient 1 binding to CBS ( Figure 4 ).…”