Instituto de Investigaciones en Materiales, Universidad Nacional Autónoma de México, Circuito Exterior S. N., Ciudad Universitaria, CP 04510, CDMX, Mexico.
Departamento de Química, División de Ciencias Básicas e Ingeniería, Universidad Autónoma Metropolitana-Iztapalapa, San Rafael Atlixco 186, Col. Vicentina, Iztapalapa. AP Postal 55-534, CP 09340, CDMX, Mexico.
Phys Chem Chem Phys. 2021 Jul 7;23(26):14224-14230. doi: 10.1039/d1cp01637g.
Psychosis is one of the psychiatric disorders that is controlled by dopaminergic drugs such as antipsychotics that have affinity for the dopamine D2 receptor (DRD2). In this investigation we perform quantum chemical calculations of two molecules [dopamine and risperidone] within a large cavity of DRD2 that represents the binding site of the receptor. Dopamine is an endogenous neurotransmitter and risperidone is a second-generation antipsychotic. Non-covalent interactions of dopamine and risperidone with DRD2 are analyzed using the Quantum Theory of Atoms in Molecules (QTAIM) and the Non-Covalent Interaction index (NCI). The QTAIM results show that these molecules strongly interact with the receptor. There are 22 non-covalent interactions for dopamine and 54 for risperidone. The electron density evaluated at each critical binding point is small in both systems but it is higher for dopamine than for risperidone, indicating that the interactions of DRD2 with the first are stronger than with the second molecule. However, the binding energy is higher for risperidone (-72.6 kcal mol-1) than for dopamine (-22.8 kcal mol-1). Thus, the strength of the binding energy is due to the number of contacts rather than the strength of the interactions themselves. This could be related to the ability of risperidone to block DRD2 and may explain the efficacy of this drug for controlling the symptoms of schizophrenia, but likewise its secondary effects.
精神病是一种由多巴胺能药物控制的精神障碍，如抗精神病药，它们对多巴胺 D2 受体 (DRD2) 具有亲和力。在这项研究中，我们对两种分子[多巴胺和利培酮]在 DRD2 的一个大空腔内进行了量子化学计算，该空腔代表了受体的结合部位。多巴胺是一种内源性神经递质，利培酮是一种第二代抗精神病药。使用分子中的原子量子理论 (QTAIM) 和非共价相互作用指数 (NCI) 分析了多巴胺和利培酮与 DRD2 的非共价相互作用。QTAIM 结果表明，这些分子与受体强烈相互作用。多巴胺有 22 个非共价相互作用，利培酮有 54 个。在这两个系统中，每个关键结合点的电子密度都很小，但多巴胺的电子密度高于利培酮，表明 DRD2 与第一种分子的相互作用比与第二种分子的相互作用更强。然而，利培酮的结合能（-72.6 kcal mol-1）高于多巴胺（-22.8 kcal mol-1）。因此，结合能的强度取决于接触的数量，而不是相互作用本身的强度。这可能与利培酮阻断 DRD2 的能力有关，这可以解释这种药物控制精神分裂症症状的功效，但也解释了它的副作用。
