Predicting the flexibility of DNA movement at the molecular level

In both physics and chemistry, the mesoscopic scale refers to the length scale on which the properties of a material or phenomenon can be studied, without having to discuss the behavior of individual atoms. In a mesoscopic model, the atomic scales are merged with the continuous scale, so they are quite difficult to develop.

A new model of DNA flexibility has been developed by Kim López-Güell, a Maths4Life student, together with Dr. Federica Battistini and under the supervision of Dr. Modesto Orozco in the Molecular Modeling and Bioinformatics laboratory at the Institute for Research in Biomedicine (IRB Barcelona). Using a low-cost computer program, the developed model, which takes into account the multimodal and harmonic approximation, provides results of unprecedented quality. The model is characterized by being precise and efficient at the computational level, which makes it an alternative to explore the dynamics of long DNA segments, having the possibility of approaching the chromatin scale.

“This work represents a milestone in the mesoscopic simulation of DNA. It presents a systematic and comprehensive study of DNA movement correlations and a new method to capture them” says Dr. Battistini, postdoctoral researcher at IRB Barcelona.

In collaboration with the “BioExcel” Center of Excellence for Computational Biomolecular Research, this work generates a greater understanding of sequencing-dependent DNA at the base pair resolution level. This topic has been studied for decades with different approaches and simplifications without achieving a multimodal model. The developed method allows a local and global description with a high precision for molecular simulations at the atomic level and experimental measurements.

The new model makes it possible to predict the flexibility of DNA movement at the molecular level. (Image: IRB Barcelona)

The movement of DNA as axis

Molecular dynamics is a computational technique that allows simulating the movement of DNA, its dimeric, trimeric or tetrameric folding, or even its interaction with proteins and drugs. In this way, scientists study processes that occur on time scales ranging from picoseconds to minutes, and that apply to molecular systems of various sizes, vital for the investigation of cell functions and disease systems.

This study clarifies how DNA movement works, with a low computational cost that can predict the flexibility and conformation of long DNA strands, which could be extended to RNA duplexes and a potential study of long polymers. The scientific community that works with nucleic acid simulations could benefit from this new model.

The research team exposes the technical details of their model in the academic journal Nucleic Acids Research, under the title “Correlated motions in DNA: beyond base-pair step models of DNA flexibility”. (Source: IRB Barcelona)