Introduction: The enzyme called dipeptidyl peptidase IV (DPP-IV) is related to the glycemic control associated with the stimulation of the pancreas to produce insulin. So, its inhibition is a good strategy for the treatment of type 2 diabetes mellitus.

Methods: In this study, we have employed molecular modeling strategies such as CoMFA, molecular docking, molecular dynamics, and binding free energy calculations of a set of DPP-IV inhibitors in order to understand the main characteristics related to the biological activity of these ligands against the enzyme.

Results: The models obtained from CoMFA presented significant values of internal (0.768) and external (0.988) validations. Important interactions with some residues, such as Glu205, Tyr666, Arg125, Ser630, Phe357 and Tyr662, were also identified. In addition, calculations of the electronic properties allowed relating the LUMO and HOMO energies with the biological activity of the compounds studied. The results obtained from the molecular dynamics simulations and the SIE calculations (ΔG) indicated that the inhibitor 40 increases the stability of the DPP-IV target.

Conclusions: Therefore, from this study, it is possible to propose molecular modifications of these DPP-IV inhibitors in order to improve their potential to treat type 2 diabetes.

简介：称为二肽基肽酶IV（DPP-IV）的酶与血糖控制有关，该血糖控制与刺激胰腺产生胰岛素有关。因此，抑制它是治疗2型糖尿病的好策略。

方法：在这项研究中，我们采用了分子建模策略，例如CoMFA，分子对接，分子动力学和一组DPP-IV抑制剂的结合自由能计算，以了解与这些配体的生物活性有关的主要特征。对抗酶。

结果：从CoMFA获得的模型显示出内部（0.768）和外部（0.988）验证的显着值。还确定了与某些残基（例如Glu205，Tyr666，Arg125，Ser630，Phe357和Tyr662）的重要相互作用。另外，电子性质的计算允许将LUMO和HOMO能量与所研究化合物的生物活性相关联。从分子动力学模拟和SIE计算（ΔG）获得的结果表明，抑制剂40增加了DPP-IV靶的稳定性。

结论：因此，从这项研究中，可能提出对这些DPP-IV抑制剂进行分子修饰，以提高其治疗2型糖尿病的潜力。