## 3 Results and Discussion
### Main Complexes Formed with Microcystins with High Affinity Scores  
#### 3.1.1 Metabolic Effects and Insulin Regulation  
The computational analysis revealed that all of the analyzed MC variants had high affinities to the CD38 protein, especially MC-LY, which showed the best docking value (\(-11.5\) kcal/mol). CD38 participates in the regulation of cell adhesion, differentiation, and cell proliferation, and has been found to alter the antiapoptotic role of insulin, induce insulin release, and the development of diabetes, and is highly expressed in the immune system [19,20]. CD38 is a transmembrane glycoprotein that, in addition to having functions as an ectoenzyme, serves as a receptor associated with the extracellular domain. It is responsible for mobilizing the Ca\({}^{2+}\) at the intracellular level and the production of ADPR, which can covalently bind to many proteins and modify their functions [20, 21, 22, 23, 24]. CD38 is made up of 300 amino acids, and their multiple enzymatic functions are executed in a single active site that presents the critical residues Glu 226, Trp 125, Trp 189, and Glu 116 [25]. Most interactions of MC-LY with CD38 are hydrophobic, and binding to the active site of CD38 occurs through Trp 125 and Trp 189 (Figure 2), while connections with highly conserved residues such as Lys 129 and Thr 221 may affect essential ectoenzyme processes such as cADDR hydrolysis, and the necessary folding for cyclization and NAD glycohydrolase (NADasa) enzyme activity [22,26]. It should be noted that CD38 has not been reported to be a target protein for MCs. However, MC-LR has been shown to impair the insulin receptor signaling pathway, and induce hyperinsulinemia and insulin resistance in mice by altering the expression of genes related to type 2 diabetes mellitus [24, 25, 26], in addition to the upregulation of several proteins such as Nduf, Ppp3 ca, Ide, Marcks, Pgk1, and Suclg1 involved in insulin secretion [19]. It has been found that MC-LR can induce partial islet dysfunction and cause T2 diabetes mellitus; this could be due to the possible binding of MCs to key CD38 residues involved in the loss of important functions such as increasing cADPR production and intracellular Ca\({}^{2+}\) release and insulin secretion, and inducing impairment of islet functions as well as activating inflammatory processes [22]. \begin{table}
\begin{tabular}{c c c c c c c} \hline  & **Short Name** & **PDB-ID** & **MC-LA** & **MC-LR** & **MC-RR** & **MC-LY** \\ \hline ADP-ribosyl cyclase/cyclic ADP-ribose & & & & & & \\ hydrolase 1 & CD38 & 3 ofs & \(-10.1\) & \(-10.1\) & \(-10.1\) & \(-11.5\) \\ Butyrylcholine & & & & & & \\ esterase & BChE & 4 xii & \(-10.5\) & \(-10.4\) & \(-10.4\) & \(-11.0\) \\ Toll-like receptor 4 & TLR4 & 3 ula & \(-10.3\) & \(-10.0\) & \(-10.1\) & \(-11.4\) \\ Toll-like receptor 8 & TLR8 & 3w3j & \(-11.5\) & \(-10.4\) & \(-10.3\) & \(-11.3\) \\ Angiotensin-I-converting enzyme & ACE & 3 nxq & \(-11.1\) & \(-11.3\) & \(-11.5\) & \(-11.3\) \\ DNA topoisomerase 2-alpha & TOP2A & 1 zxm & \(-10.7\) & \(-10.6\) & \(-10.6\) & \(-11.1\) \\ Induced myeloid leukemia cell & & & & & & \\ differentiation protein Mcl-1 & & 5 lof & \(-10.7\) & \(-10.9\) & \(-10.2\) & \(-10.6\) \\ Hemoglobin subunit alpha & HBA & 3b75 & \(-11.2\) & \(-10.2\) & \(-11.4\) & \(-11.0\) \\ Apoptosis regulator Bcl-2 & BCL2 & 2w3l & \(-10.6\) & \(-10.6\) & \(-10.2\) & \(-10.9\) \\ Heat shock protein HSP 90-alpha & HSP90 & 2 qg0 & \(-10.2\) & \(-10.1\) & \(-10.9\) & \(-10.9\) \\ Serine/threonine-protein kinase 26 & MST-4 & 3 ggf & \(-11.0\) & \(-10.5\) & \(-10.2\) & \(-10.9\) \\ Catalase & CAT & 1 dgb & \(-10.7\) & \(-10.4\) & \(-10.4\) & \(-10.7\) \\ Transthyretin & TTR & 1 ict & \(-10.8\) & \(-10.2\) & \(-10.2\) & \(-10.6\) \\ Calcium/calmodulin-dependent & & & & & & \\ serine/threonine kinase & & & & & & \\ Aminopeptidase N & AMPN & 4 fyr & \(-10.5\) & \(-10.3\) & \(-10.3\) & \(-10.3\) \\ \hline \end{tabular}
\end{table}