Hello!
I have performed umbrella sampling to study the covalent bond formation between a ligand and a Cysteine residue. Where Histidine is a proton-donating residue to complete a reaction. I have successfully created PMF and have the correct overlapping windows.
I now want to display the imaginary frequencies and displacement vectors but cannot understand these. Do I need to find the Radius of Gyration or RMSD vs. PMF? Where do I find the imaginary frequencies? and How do I draw the displacement vectors?
Your guidance will be appreciated.
Regards,
Umbrella Sampling is a simulation method used in molecular dynamics to calculate the potential of mean force (PMF) along a reaction coordinate of interest. This PMF can be used to calculate thermodynamic quantities such as free energy and enthalpy.
The calculation of imaginary frequencies and displacement vectors from Umbrella Sampling requires a series of steps, including the following:
Preparation of the simulation: Umbrella Sampling requires the definition of windows along the reaction coordinate and the application of a biasing potential to each window to sample the conformations of the system.
Calculation of the PMF: The PMF can be calculated from the distribution of configurations in each window by using the weighted histogram analysis method (WHAM) or other similar methods.
Normal mode analysis: The PMF can be used as a potential energy surface (PES) for a normal mode analysis, which involves the calculation of the eigenvalues and eigenvectors of the system's Hessian matrix. The eigenvalues represent the frequencies of the normal modes, and the eigenvectors represent the displacement vectors.
Imaginary frequency analysis: The normal modes with negative frequencies are associated with unstable conformations and correspond to imaginary frequencies. The magnitude of these frequencies can be used to estimate the rate of conformational changes, such as conformational transitions or protein folding/unfolding.
Displacement vector analysis: The displacement vectors can be used to visualize the normal modes and the direction of the conformational changes associated with each normal mode. This can provide insight into the mechanism of the reaction and the key residues involved in the transition.
It's worth noting that Umbrella Sampling and the subsequent analysis can be computationally intensive, and it is essential to choose the appropriate parameters and simulation conditions to ensure accurate results.
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