AMBER Archive (2005)

Subject: Re: AMBER: Quantifying DNA perterbation

From: Thomas Cheatham (cheatham_at_chpc.utah.edu)
Date: Tue Nov 15 2005 - 23:55:55 CST

> Does anyone know of a method to quantify how much DNA has been perterbed
> during a MD run? I have done MD simulations of DNA with a cross-linker of

This is a difficult question to answer since there are so many ways to
analyze perturbations in DNA structure. Your first question to ask
yourself is what do you mean by "perturbation" in DNA structure?
(what about changes in dynamics? energetics? sampling?)

- change in helicoidal parameters (Curves, 3DNA, ...)
- change in backbone angles / sugar pucker / base-base interactions (ptraj)
- change in bending/end-to-end length (ptraj for distances)
- RMSd changes (ptraj for RMSd)
- MM-PBSA to estimate differences in approximate free energies with time (MM-PBSA)
- change in hydrogen bonding of base pairs (ptraj hbond)
- changes in solvation (ptraj grid vs. radial vs. hbond)
- changes in ion association (ptraj hbond)
- differences in MSD (mean squared displacements, B-factors)
- changes in bond correlations / order parameters (ptraj, correlation)
- changes in quasi-harmonic entropy estimates (ptraj, matrix)
- changes in local DNA structure (i.e. base-base interactions or hbonding
or some other local indicator of the perturbation)
- look at movies (ideally smoothed in some manner such as by using the
runningaverage command in ptraj) to see differences between
runs/trajectories.

For each of the changes you observe, you will have to show that they are
statistically significant either through multiple independent MD
simulations or block averaging or some other means. In general, there is
no perfect measure of a perturbation; you have to visualize changes
somehow and put this in the context of a measurable quantity (to convince
experimentalists that the change you see is real). Running the
simulations is the easy part; actually figuring out what they mean is
very hard.

--tom

\-/ Thomas E. Cheatham, III (Assistant Professor) College of Pharmacy
-/- Departments of Med. Chem. and of Pharmaceutics and Pharm. Chem.
/-\ Adjunct Asst Prof of Bioeng.; Center for High Performance Computing
\-/ University of Utah, 30 S 2000 E, SH 201, Salt Lake City, UT 84112
-/-
/-\ tec3_at_utah.edu (801) 587-9652; FAX: (801) 585-9119
\-/ BPRP295A http://www.chpc.utah.edu/~cheatham

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