student0618 发表于 2024-6-20 23:58
Past members in my group used the nonbonded model with Li-Merz ion parameters for the active site of ...

非常感谢您！

Past members in my group used the nonbonded model with Li-Merz ion parameters for the active site of human cyclic nucleotide phosphodiesterase, only hydroxide parameters from literature/resp fitting (not a bacteria phosphotriesterase of your case, but has a similar two-metal site and a bridging hydroxide proposed to be the attacking nucleophile. Similar to the suggested mechanism from the original paper of the PDB you use, but the coordination geometry could differ). At that time this nonbonded model was sufficient for our purpose. However it was before 2012, over 10 years ago, on a different system than yours. I am not sure if this could apply to your system for your purpose of modelling.

Technically mcpb.py can be used to prepare or derive parameters for many metalloenzyme, mainly for the bonded model. Again I am not sure if the bonded model or nonbonded model is better for your system and your purpose, you may refer to some more recent literature of your system to see if anyone has a reasonable way to model it, or test it yourself to see if it gives you something close to crystal structure in MD.

( 抱歉，我不太擅長用中文寫有技術性專有名詞的句子，所以用英文回)

student0618 发表于 2024-6-20 18:40
Not sure if its the reason, but I observed two possible issues in your syetem.

1. from the refer ...

Can I use mcpb.py to replace the water molecule H2O with a hydroxide ion OH- as the bridging ligand between two zinc ions?

student0618 发表于 2024-6-20 18:40
Not sure if its the reason, but I observed two possible issues in your syetem.

1. from the refer ...

thanks！

Not sure if its the reason, but I observed two possible issues in your syetem.

1. from the reference publication of PDB entry 1HZY (check the Literature box within PDB site or abstract at https://pubs.acs.org/doi/10.1021/bi002661e):

... and a carboxylated Lys 169. Both Lys 169 and a water molecule (or hydroxide ion) serve to bridge the two zinc ions together.

Lys169 (Lys135 in your gro) is carboxylated, but you modelled the lysine and carboxylate separately.

2. A side note here, the oxygen between two metal ions in phosphotriesterase/phosphodiesterase is commonly modelled as hydroxide ion (OH-), maybe also check if you should do this for your complex.