Trying to run QM/MM simulation with calcium binding protein

In summary, a graduate student is having trouble getting a QM/MM simulation to converge, and has tried a few methods with little success. He is using Orca, but is considering trying a different method if the current one does not converge. The system is multi-configuration and the QM/MM simulation is failing to converge; however, if the simulation is started with a low level of theory and continues to grow more accurate, it may be possible to use the new MOs from the earlier calculation as an initial guess for a production run using a larger basis set and/or a higher level of theory.
  • #1
nisler.1
2
0
Hello everyone, I'm a graduate student in a biophysics lab. I'm trying to run a QM/MM simulation with a protein that binds 3 Ca2+ ions, and as such I am having a devil of a time getting the SCF to converge. I've tried DIIS, KDIIS, damping, and a few other methods to try to get convergence with not much luck. The couple of times it has converged, it was after more than 100 iterations, which is just too expensive. Does anyone have any suggestions of things I could try? It doesn't matter much, but I'm using Orca for the QM portion. Thanks a bunch.
 
Chemistry news on Phys.org
  • #2
Plot your energy after each SCF cycle. Are they oscillating or are they going down continually? If they're going down continually, then you probably just need more SCF cycles to reach convergence (I'm assuming the program terminates after a preset number of SCF cycles--which you should be able to adjust). If they're oscillating, you might need to loosen your convergence criteria, at least for preliminary runs. Sometimes if you start with a crappy initial guess for your molecular orbitals, it just takes a while and there's nothing you can do about it. But if you can get it to converge once, you can usually use these new MOs for a better initial guess. I'm sure there are ways to do this in Orca; it's a pretty robust program.

Of course, all this assumes that your system is reasonably well-behaved. If you have a system which is inherently multi-configuration and you're running an HF-type calculation, your SCF runs will fail to converge because your model isn't a reasonable approximation of the system.
 
  • #3
TeethWhitener said:
But if you can get it to converge once, you can usually use these new MOs for a better initial guess.
I just realized this made no sense when I read it to myself. What I meant was: 1) get the system to converge with an obscenely low level of theory/small basis set like HF/STO-3G or 3-21G. Then 2) use the MOs from this calculation as an initial guess for a production run with a bigger basis set and/or a higher level of theory.
 

1. What is a QM/MM simulation?

A QM/MM simulation is a computational method that combines quantum mechanics (QM) and molecular mechanics (MM) to study the behavior and interactions of molecules. It allows for a more accurate and detailed description of chemical reactions and properties compared to using either QM or MM alone.

2. What is a calcium binding protein?

A calcium binding protein is a type of protein that has a specific binding site for calcium ions. These proteins are important for regulating various biological processes, including muscle contraction, nerve function, and enzyme activity.

3. How is a QM/MM simulation with calcium binding protein performed?

A QM/MM simulation with calcium binding protein involves using a combination of quantum mechanics calculations to model the behavior of the calcium ions and molecular mechanics calculations to model the behavior of the surrounding protein molecules. The two methods are then combined to simulate the interactions between the calcium ions and the protein.

4. What are the challenges of running a QM/MM simulation with calcium binding protein?

One of the main challenges of running a QM/MM simulation with calcium binding protein is the computational complexity and the high level of technical expertise required. Additionally, accurately modeling the interactions between the calcium ions and the protein can be difficult due to the dynamic nature of the binding site and the potential for multiple binding sites.

5. What are the potential applications of QM/MM simulations with calcium binding protein?

QM/MM simulations with calcium binding protein have a wide range of potential applications in various fields, including drug discovery, protein engineering, and understanding biological processes. These simulations can provide valuable insights into the mechanisms of calcium binding and the effects of different mutations or ligands on the protein's function.

Hot Threads

Recent Insights

Back
Top