Lecithin:cholesterol acyltransferase protein (LCAT) promotes the esterification reaction between cholesterol and phospholipid derived acyl chains. Positive allosteric modulators have been developed to treat LCAT deficiencies and, plausibly, also cardiovascular diseases in the future. The mechanism of action of these compounds is poorly understood. Here computational docking and atomistic molecular dynamics simulations were utilized to study the interactions between LCAT and the activating compounds. Results indicate that all drugs bind to the allosteric binding pocket in the membrane-binding domain in a similar fashion. The presence of the compounds in the allosteric site results in a distinct spatial orientation and sampling of the membrane-binding domain (MBD). The MBD's different spatial arrangement plausibly affects the lid's movement from closed to open state and vice versa, as suggested by steered molecular dynamics simulations.

中文翻译：

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卵磷脂：胆固醇酰基转移酶的正构构调节剂可调节膜结合结构域的方向并改变其空间自由能分布

卵磷脂：胆固醇酰基转移酶蛋白（LCAT）促进胆固醇与磷脂衍生的酰基链之间的酯化反应。积极的变构调节剂已被开发用于治疗LCAT缺乏症，以及将来可能治疗的心血管疾病。这些化合物的作用机理了解甚少。在这里，通过计算对接和原子分子动力学模拟来研究LCAT和活化化合物之间的相互作用。结果表明，所有药物均以相似的方式与膜结合结构域中的变构结合袋结合。化合物在变构位点中的存在导致明显的空间取向和膜结合结构域（MBD）的采样。MBD的不同空间排列可能会影响盖子的