A simple low-cost simulation protocol for approximate localization of structural water molecules in DNA oligonucleotides

Amarílis De V Finageiv Neder,Marçal De Oliveira Neto

doi:10.1590/s0103-50532005000400017

Abstract

Using a computational low-cost protocol by combining molecular mechanics energy minimization and molecular dynamics employing the OPLS-AA force field, we were able to reproduce the main structural features of the first hydration shell of double-helix DNA hetero-oligonucleotides in the A (1DPL) and B-conformations (1DPN and 1ENN), whose coordinates are available with atomic resolution from crystallographic data. Our simple protocol also reproduced the main hydration patterns of DNA homo-oligonucleotides in the B-conformation [(AT)12 and (CG)12], obtained before by computer simulation using a longer and more sophisticated molecular dynamics protocol. A preliminary model of the first hydration shell of oligonucleotides may be very useful to those interested in performing quantum-mechanical calculations of systems where hydration features are unknown at the molecular level; the model may also be used by crystallographers during refinement steps.

Highlights

Water is a ubiquitous molecule in the biological environment and is considered to be an intrinsic component of the structure of nucleic acids
Many ligands, such as amino acids, drugs or even other nucleotides, interact with nucleic acids either through a water bridge or by replacing structural water molecules bound to specific sites or, most commonly, by both types of contacts.[1]
We present a simple low-cost protocol involving mixed steps of molecular dynamics (MD) and energy minimization (EM) calculations which can reproduce the main features of the hydration profile of nucleic acid oligomers as described by crystallographic studies

Summary

Introduction

Water is a ubiquitous molecule in the biological environment and is considered to be an intrinsic component of the structure of nucleic acids (structural water molecules). Many ligands, such as amino acids, drugs or even other nucleotides, interact with nucleic acids either through a water bridge or by replacing structural water molecules bound to specific sites or, most commonly, by both types of contacts.[1] the preferential hydration sites of nucleic bases are quite conservative according to comparative crystallographic data,[2] different nucleotide sequences,[3] base compositions,[4] and conformations[5] affect hydration in a very complex manner.

Methods

Results

Conclusion