请问大家进行完分子对接后怎么进行分子对力学模拟验证结果是否准确？

s2023

本人是小白，想要对我的蛋白进行理性设计，看文献和网上教程用autodock进行完分子对接后，获得了一个最优构象组合，不知道后续具体怎么进行分子对力学模拟？怎么分析对接结果是否可靠？
ps：蛋白是αfold2模拟的，直接拿来进行对接了
谢谢大家！

rpestana94

If you are using an alphafold model, first before docking I suggest to run a molecular dynamic, to get an stable conformation (this also help to validate your model is stable enough), using something like propka to get right protonation, then docking, then molecular simulation, try to find some experimental evidence to try to compare with your simulation, the usual analysis you find in literature are RMSD, RMSF, radius gyration, hydrogen bonds.  You can try also with MMPBSA.

s2023

rpestana94 发表于 2023-2-14 17:26
If you are using an alphafold model, first before docking I suggest to run a molecular dynamic, to g ...

谢谢老师，还想请问一下分子对接后做分子动力学模拟用到的配体是用对接结果的复合物拆开来的配体，还是从pubmed上下载的该配体就行

rpestana94

s2023 发表于 2023-2-14 06:01
谢谢老师，还想请问一下分子对接后做分子动力学模拟用到的配体是用对接结果的复合物拆开来的配体，还是从 ...

you should use your docking results, because the docking give you an "optimal" position for interaction, so the results of the docking should be the starting point of the simulation

sobereva

用于复合物动力学模拟的初始结构显然是对接得到的

但要注意对接程序对氢的考虑和实际力场的差异，比如对接程序不考虑非极性氢，但你用比如AMBER14SB+GAFF的全原子力场的组合去模拟复合物，就相差了极性氢。如果你用比如sobtop（http://sobereva.com/soft/Sobtop）产生GROMACS的配体的拓扑文件，并且是把对接完的配体部分抠出来处理，就必须把对接的结构里配体的氢都补全了才行。

s2023

rpestana94 发表于 2023-2-14 20:37
you should use your docking results, because the docking give you an "optimal" position for intera ...

好的，谢谢老师

s2023

sobereva 发表于 2023-2-15 06:12
用于复合物动力学模拟的初始结构显然是对接得到的

但要注意对接程序对氢的考虑和实际力场的差异，比如对 ...

好滴，谢谢sob老师