在炼化结合自由能预测中服多重结合姿势:β-环极素宿主-客体 SAMPL9 盲目的挑战
Sheenam Khuttan1,2, Solmaz Azimi1,2, Joe Z Wu1,3
1Department of Chemistry, Brooklyn College of the City University of New York, New York, USA. egallicchio@brooklyn.cuny.edu.
Physical chemistry chemical physics : PCCP
|September 7, 2023
概括
炼化转移方法 (ATM) 准确地预测了环极素的宿主-客人结合亲缘关系,克服了药物设计模拟中复杂的结合姿势和化学形式等挑战.
科学领域:
- 计算化学是一种计算化学.
- 分子建模分子建模
- 药物发现 药物发现
背景情况:
- 宿主-客人复杂化在药物设计中至关重要.
- 准确预测结合的自由能量仍然是一个重要的计算挑战.
- 提亚客和环极主体呈现复杂的结合场景.
研究的目的:
- 用化学转移方法 (ATM) 预测表亚客和环氧德克斯主体的结合自由能量.
- 为了评估定制固定部分电荷力场在主机-客户端绑定预测中的性能.
- 解决包括多种化学形式和结合姿势在内的计算挑战.
主要方法:
- 应用炼化转移方法 (ATM) 进行具有约束力的自由能量计算.
- 使用定制的固定部分充电力场.
- 采用元动力学加速的 conformational 采样,以克服 conformational 陷.
- 对每个物种和姿势进行了一系列绝对和相对结合的炼化步骤.
主要成果:
- 盲目的预测量性地复制了对β-cyclodextrin宿主的实验亲和关系.
- 预测显示对甲基化环氧二衍生物的适度一致.
- 证明了先进的采样技术对于可靠的自由能源估计的必要性.
结论:
- 该研究强调了在in silico药物设计中获得可靠的自由能量数据的复杂性.
- ATM和先进的采样方法是解决挑战性主机-客户系统的有效工具.
- 这些发现为药物发现的计算策略提供了洞察力,这些策略涉及环德林相互作用.
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