Double decoupling absolute binding free energy simulations require an intermediate state at which the ligand is held solely by restraints in a position and orientation resembling the bound state. One possible choice consists of one distance, two angle, and three dihedral angle restraints. Here, I demonstrate that in practically all cases the analytical correction derived under the rigid rotator harmonic oscillator approximation is sufficient to account for the free energy of the restraints.

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关于绝对结合自由能计算中约束的解析修正

双解耦绝对结合自由能模拟需要一个中间状态，在该状态下配体仅通过约束保持在类似于结合状态的位置和方向。一种可能的选择包括一种距离、两种角度和三种二面角约束。在这里，我证明在几乎所有情况下，在刚性转子简谐振子近似下导出的解析校正足以解释约束的自由能。