VMD-L Mailing List

From: Francesco Pietra (chiendarret_at_gmail.com)
Date: Sun Feb 06 2022 - 01:59:52 CST

Hi all
Hope not to bother you with an issue that I have already posed in part.

I am dealing with a "small molecule" ligand (actually C29 with several
oxygens and protons and long side chains that emerge from a central
tricyclic core) surrounded by nucleotides in two different situations.
Either standard nucleotides only, or a mixture of standard and
naturally-occurring nucleotides. The two situations, from the same
eukaryotic RNA, fungal or human, in the two cases, are described by
diffraction data at fairly good resolution, better for case of modified
nucleotides. There are also proteins, but far away from the ligand binding
site.

For all above nucleotides topology and parameters are available from
CHARMM36.The ligand was parameterized with the CGenFF, of a version
compatible with the CHARMM36 FF used for the nucleotides and proteins.

What occurs (rechecked several times) is that, in the case of only standard
nucleotides, the ligand maintains perfectly its bond-to-bond structure and
fairly well also the conformation of the side chain backbone on
minimization, heating, NVT and NPT. Just what one expects on carrying out
MD.

When modified nucleotides are present, the conformation of the ligand is
altered heavily on minimization. Curiously, the most exposed C-H moieties
(both CH3 and CH2) completely loose their sp3 and sp2 characters. Methyls
are show with CH3 in a single plane. Heating alters also the conformation
of the backbone, while on NPT the molecule cannot be recognized any more.
The environment of nucleotides (standard only or standard-modified mixture)
was perfectly conserved on all above procedures.

To anyone who had the patience to go through this post I am asking for a
suggestion about possible causes of all that. After a patient dealing with
such affairs, I am short of imagination. The parameterization of the
ligand was carried out on several different servers; in any case the
minimization/MD outcome was of the type described above. Although the
parameterization of the ligand was not much refined, what occurs on
minimization when modified nucleotides are present must have different
causes.

Thanks
francesco pietra