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help please! Thanks! about the parameter selection
#4883 01/07/05 08:53 AM
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Help ! Please!
I am trying to compute the binding-energy of protein-protein interaction. Because of some special request, we want to write program by ourselves with the MMFF. The constituent terms of binding energy is E_vdw, E_ele and E_hbond. With the reference to the mmff, we can get the format of energy easily. Now, we meet problem when we choose the parameters to be used in computing the energy.
The structure data comes from PDB file. The hydrogen coordinate is missing. Whether or not is the hydrogen atom considered separately in MMFF. Such as
HOS 33 H ON OXYGEN ATTACHED TO SULFUR(a simple defination of atom type in MMFF)
Does it mean the Hydrogen atom or H-O group?

Secondly, the energy of salt bridge coming from amino acid with positive or negative charge can be computed according to the electrostatic interaction?

Thanks very much!

Thanks very much!

Re: help please! Thanks! about the parameter selection
lwwd #4884 01/07/05 06:57 PM
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rmv Online Content
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I've found the MMFF implementation in CHARMM to be highly problematic, and none of implementors are available to fix problems or field questions. PSF generation and other operations are radically different from the use of standard CHARMM parameters, and both patching and adding H atoms were frustrating exercises. If you want to use MMFF, I wouldn't recommend CHARMM; if you want to use CHARMM, I wouldn't recommend MMFF.


Rick Venable
computational chemist

Re: help please! Thanks! about the parameter selection
rmv #4885 01/08/05 01:36 AM
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Really thanks for your reply!
As your meaning,If I want to compute the vdw interaction energy with the format used in charmm, best way is to use the standard charmm parameter set,not MMFF,right?

Re: help please! Thanks! about the parameter selection
lwwd #4886 01/08/05 06:35 PM
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I spent quite a bit of time trying to set up PSFs for a series of drug molecules bound in an enzyme active site using MMFF in CHARMM and never got to the point where I could get reliable energy evaluations. Every problem I solved introduced a new problem; eventually, I had to drop the project as a consequence. It's a shame, as 2 of the drugs were Celebrex and Vioxx; the dilemma was that standard CHARMM parameters weren't available for a number of the functional groups (esp. sulfonamide) and would take too long to develop, so I gambled on MMFF and lost. Adding new molecules with unparametrized functional groups is one of the biggest problems confronting CHARMM users, mostly because of the amount of effort involved.


Rick Venable
computational chemist

Re: help please! Thanks! about the parameter selection
rmv #4887 01/10/05 01:53 AM
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lwwd Offline OP
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hi rmv,
In your reply, you mention the reliable energy evaluations. What standard you use in evaluating the computational energy? Comparing the computational interaction energy with the practical affinity existing between the medicine molecule and enzyme?
My research work focuses on the interaction between the protein antibody and antigen. As i understand, the vdw interaction, the hydro-bond and salt bridge are my mainly considering consideration. Maybe the situation of interaction bewteen the protein is more simple than the interaction of medicine molecule and enzyme, isn't it?

Thank you for your help. I benefit from your reply very much

Re: help please! Thanks! about the parameter selection
lwwd #4888 01/10/05 04:51 PM
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I meant free of significant CHARMM errors or warnings; I never got a result I could trust, period.


Rick Venable
computational chemist


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