Asked 19th Nov, 2016

Molecular dynamics and conformation analysis?

I have performed structure prediction for disordered region (75 aa) of a protein and performed molecular dynamics for 10 nano seconds using relevant force field. How to obtain the most stable conformation or state  from the performed MD results and a small epitope region of 10-mer is also available as crystal structure for the comparisons.

All Answers (3)

19th Nov, 2016
Hiqmet Kamberaj
International Balkan University
The most stable state corresponds to the minimum of free energy (either Helmholtz free energy in NVT or Gibbs free energy in NPT MD simulations.) To determine the free energy landscape, however, is a difficult problem, because if you see it as a function of all degrees of freedom of the system, then it becomes very difficult to calculate it and to visualize. Therefore, often the problem reduces to determining the so-called reaction coordinates (or collective coordinates), which will define a free energy landscape, where you can perform a minimum free energy search for obtaining the most stable state. Determining the collectives coordinates will depend on the system and problem, however some choices can be suggested, for example, backbone dihedral angles (Phi,Psi), root mean square deviation and radius of gyration, first two or three principal component analysis (PCA). Then, the free energy can be constructed as a function one, two or three of these reaction coordinates (not very often more than two) and perform a minimum search for determining the most stable state.
I hope this could help you.
1 Recommendation
24th Nov, 2016
Sara Ibrahim Omar
Proteic Bioscience
Hi Arun,
Intrinsically disordered proteins do not have prominent structures. I am actually surprised that you say there is a crystal structure for a part of that protein, unless that region is not part of the disordered region of the protein. Also, 10 ns is not long enough to capture the different conformations of a protein.
For a more general case, you can use clustering of the different conformations in the trajectory based on their structure and use the representative structure of the different clusters to present the prominent conformations of the proteins. Again, you need a longer simulation to use this protocol.
6th Dec, 2016
Poonam Pandey
University of Maryland, Baltimore
Hi arun, 
You can perform marcov state model based clustering  of trjectory to find prominent conformation of the protein. Please check the link:

Similar questions and discussions

How to solve Amber Leap topology and coordinate preparation error "maximum coordination exceeded " ?
1 answer
  • Priya MuruganPriya Murugan
Hi Researchers,
I'm using PDB file 5IBE protein structure with co-crystallised ligand 69M for molecular dynamic simulation with AMBER. It is a complex protein with a heme cofactor.
For the preparation of parameter for my non-standard residue ligand 69M,
Firstly, I generated a mol2 and frcmod file using Antechamber for the cocrystallized ligand.
After that, I loaded the generated parameter files (mol2, frcmod -missing parameters) into Leap to enable the Leap to recognise my ligand as a unit and saved the ligand's parameters as library, prmtop and rst7 files. After I completed these steps, I was ready to create the topology and coordinate files for my protein with the cocrystallised ligand (5IBE_69M.pdb).
so, first, I ran Tleap,
then, added the script as followed:
source leaprc.proteinff14SB, source leaprc.gaff,
then I loaded frcmod file as loadamberparams 69M.frcmod
load library file as loadoff 69M.lib
then, loaded my protein pdb file as complex = loadpdb 5IBE_69M.pdb
But, at this last step the I was unable to generate toplogy file and couldn't save pdb as 5IBE_69M.prmtop and 5IBE_69M.rst7 files ?
and I got this kind of errors:
Bond: Maximum coordination exceeded on .R<69M 397>.A<01 2> .R<69M 397> .A<H17 43>
ATOMS NOT BONDED : .R<69M 397> .A<01 2> .R<69M 397> .A<H17 43>
FATAL ERROR --------------------------------------------------------------------------------------------
!FATAL: In file [atom .c], line 445
!FATAL: Message: bondAtomProblem found
I have attached the error file here. please have a look at it and let me know the problem. Your small help can be a huge guide for me to keep stepping forward in my work.
Thank you in advance.
How can I run a vacuum calculation in Gromacs version 5.1.3? I'm having a lot of trouble getting the necessary .tpr file?
8 answers
  • Adron UngAdron Ung
So the command I want execute is in this short little document:
being $ gmx mdrun -s input.tpr -rerun configuration.pdb
The issue is that while I able to use a special forcefield, create a topology file, and a .gro file with $gmx pdb2gmx ... -water none", I am not able to create the .tpr file.
I had high hopes that by using grompp with this .mdp file, I could create the .tpr file, and then do an mdrun. But I'm getting a lot of errors which I don't understand with respect to Verlet Lists and incompatibility with the latest version of Gromacs 5.1.3.
It would be easy if I was doing a solvation. But I need to do this vacuum, and I'm surprised why that's so difficult. Is it possible to create a .tpr file without an .mdp file? My superior would like me to figure out a sequence of commands that works and then we can loop through several files, and do some energy statistics.
Please. Would someone please help me?
Thank you.

Related Publications

An empirical potential based quasicontinuum theory (EQT) is proposed to predict the structure, concentration, and various potential profiles of water in confined environments. EQT seamlessly unifies the continuum theory given by the Nernst-Planck equation and the atomistic theory governed by interatomic potentials. In particular, the interatomic po...
Got a technical question?
Get high-quality answers from experts.