[gmx-users] Simulation of wild and mutant types of HSA protein

Justin Lemkul jalemkul at vt.edu
Tue Jun 3 14:39:20 CEST 2014

On 6/3/14, 8:19 AM, Negar Parvizi wrote:
> Dear Gromacs users
>> I have a question about protein simulation in Gromacs. We are interested in the effect of single point mutation on the structure of HSA (human serum albumin) protein.
>> We selected a pdb file for wild type HSA and submitted it for MD simulation.
>> One of the mutatns of HSA is called R218H. To simulate this mutant which of the following ways is correct?
>> 1) we found a pdb file for this mutant. It has 14 residues missed which we used modeller to add these residues. Now we
>> can simulate this protein.
>> 2) One of our friends suggested to take the wild type HSA and only substitute the residue 218 to create the mutant form of HSA and to use swiss pdb viewer to get the appropriate pdb file for that.
>> Now I wanted to know which way is correct? is there any difference between these two approaches?
>> Is it necessary to take the pdb file for the mutant and add the missed residues or only with the substitution of that single residue in the wild type HSA pdb file we can make the mutant pdb file?

A few points to consider are whether or not the mutation changes the structure, 
and to what extent the modeled segment differs from the WT structure (and I 
suppose, whether or not the mutation plays any role in determining that structure).

The simplest approach is what you did in (2).  It's easy and pretty robust.  You 
just have to simulate long enough to make sure you're observing any implications 
due to the mutation.  You can compare its RMSD with the crystal structure of the 
mutant (for residues with assigned positions), though that's not the be-all, 
end-all of verification, but it is simple.



Justin A. Lemkul, Ph.D.
Ruth L. Kirschstein NRSA Postdoctoral Fellow

Department of Pharmaceutical Sciences
School of Pharmacy
Health Sciences Facility II, Room 601
University of Maryland, Baltimore
20 Penn St.
Baltimore, MD 21201

jalemkul at outerbanks.umaryland.edu | (410) 706-7441


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