Book of Abstracts: Albany 2009
June 16-20 2009
© Adenine Press (2008)
RNA Simulations - Part 2: Molecular Dynamics Simulations of RNA Fragments at Hydrogen Resolution
Hydrogen atoms (H) represent about 35% of the total number of nucleic acids atoms. They play an active role in most molecular recognition phenomena, through the formation of intra and inter-molecular H bonds often involving solvent molecules. Unfortunately, experimental methods rarely allow localizing hydrogen atom positions.
Here, we propose to fill such experimental gaps by extracting hydrogen atom positions from nucleic acid molecular dynamics (MD) simulations. By using several MD simulations of a regular RNA duplex containing G=C and G·U pairs, we mapped first hydration shell hydrogen atom positions around each base pair following SwS protocols (see reference). The most probable hydrogen atom positions can be deduced from calculated nuclear-density maps analogous to high-resolution neutron diffraction maps (see figure). For example, such maps reveal most of the direct solute-solvent and some solvent-solvent H bonds. They show also an unexpected level of H-bond dynamics for the highly conserved shallow groove water molecule that links the two bases of a G·U pair. Hence, calculated nuclear-density maps allow reconstructing H-bond networks around nucleic acid fragments involved or not in the binding of other RNA or DNA fragments, proteins or small ligands. The precise knowledge of these H bond networks can lead to improved ?rational? drug design strategies in which ligand functional groups can be more efficiently fitted into solvent atom density maps.
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