[gmx-users] Ring planarity

[Justin Lemkul]

On 6/9/16 12:16 PM, Mohsen Ramezanpour wrote:
> Dear Gromacs users,
>
> I am working on a Protein-drug interaction problem.
>
> The small molecule has a cytosine ring.
>
> Based on QM calculations and PDB database, The structure for this ring
> should be planar. However, doing simulations the the ring is not completely
> planar . Besides, the NH2 group on it will make an angle with the ring
> overall plane.
>
> I was wondering if I should 1) halt the 1-4 interactions among the ring
> atoms with neighbour atoms out of ring, 2) apply more strong improper
> dihedrals force constants, or 3) this kind of deviations (from optimized
> geometry in gas phase) is Ok. The latter case (#3) can be justified because
> in the presence of protein and water, the overall energy of system might be
> more favourable in this deformed structure, although a high energy might be
> needed to deform a ring.
>
> The same for NH2 group connected to the ring. Should I force it to stay in
> the plane or let it go as it prefers?
>

The QM geometry of exocyclic amines should *not* yield a planar structure.  In 
fact, for Ade, Gua, and Cyt, the pyramidal character of their amines can be 
considerable.  In solution, however, this out-of-plane deviation should be 
smaller as it is damped by the surrounding solvent.

Most, if not all, high-quality MM force fields should handle this correctly (I 
know CHARMM does, and likely AMBER, too).  So if whatever parameters you're 
using for the cytosine moiety don't yield a proper description of the dynamics, 
look to something trustworthy.  Cyt should not be perfectly planar in solution, 
but the amplitude of the deformation should be pretty small.

-Justin

-- 
==================================================

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

Department of Pharmaceutical Sciences
School of Pharmacy
Health Sciences Facility II, Room 629
University of Maryland, Baltimore
20 Penn St.
Baltimore, MD 21201

jalemkul at outerbanks.umaryland.edu | (410) 706-7441
http://mackerell.umaryland.edu/~jalemkul

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