Molecular mechanics studies on poly(purine).poly(pyrimidine) sequences in DNA: polymorphism and local variability

Area of Science:

• Molecular Biophysics
• Computational Biology
• Structural Biology

Background:

• DNA exists in various helical forms, including A- and B-types, which can differ significantly from fiber models.
• Understanding the energetic preferences and structural nuances of these DNA conformations is crucial for molecular biology.

Purpose of the Study:

• To perform energy minimization on poly(purine).poly(pyrimidine) DNA sequences using molecular mechanics.
• To extensively scan conformational space and compare different helical models (right-handed A/B, left-handed).
• To analyze local structural variability and compare refined models to fiber DNA structures.

Main Methods:

• Energy minimization using the AMBER (Assisted Model Building and Energy Refinement) program.
• Study of five different helical models: three right-handed (A-type, B-type) and two left-handed.
• Detailed analysis of torsion angles and other structural parameters (e.g., base-pair tilt, wedge roll).

Main Results:

• Right-handed A- and B-type helices were found to be energetically slightly preferred over left-handed helices for the studied sequences.
• Refined A-form structures showed higher unit rise and lower unit twist and base-pair tilt compared to fiber models.
• Refined B-form structures closely resembled fiber B-form helical parameters, despite variations in torsion angles.

Conclusions:

• The refined A-form DNA models align more closely with experimentally observed A-form structures in oligonucleotide crystals.
• The refined B-form DNA models are consistent with fiber B-form DNA, with no significant helical curvature observed for the studied sequences.
• This study provides insights into the conformational preferences and structural characteristics of different DNA helices.