Self-Assembly of G-quadruplexes using Molecular Dynamics simulations

Summary

Motivation

The structural dynamics of nucleic acid G-quadruplexes (GQs) are of critical biological and therapeutic interest due to their regulatory roles in telomere maintenance, oncogene expression, and potential as drug targets. GQs are unique secondary structures stabilized by guanine tetrads, with folding and unfolding pathways playing a central role in their functional versatility.

Despite extensive experimental and computational studies, the atomic-level mechanisms governing these transitions remain poorly understood.

This gap in knowledge represents a significant hurdle in leveraging GQs for therapeutic development or understanding their role in cellular processes.

Classical molecular dynamics (MD) simulation is the computational method of choice to study the dynamics behaviour of biomolecules and the way they interact, providing detailed atomic structural dynamics information occurring on the microsecond time scale that cannot be accessed by experimental measurements.

In this project MD simulations will be performed to evaluate folding and unfolding pathways of GQs. Experimental validation will be generated from Circular Dichroism experiments.

Underlying aim

The overarching objective is to elucidate the folding and unfolding mechanisms of G-quadruplexes. The rationale is that combining high-resolution MD simulations with experimental validation by Circular Dichroism (CD) will provide unprecedented insights into the mechanisms of GQ folding.

Methods to be used

*              MD simulations.

*              Circular Dichroism.

Impact

We will utilize the Northern Ireland High Performance Computing (NI-HPC) facilities to utilize and develop advanced MD methods to evaluate GQ self-assembly processes, including folding, unfolding, and intermediate state formation.

By integrating cutting-edge computational resources with experimental validation, this project aims to bridge the knowledge gap in GQ dynamics and deliver transformative insights into their structural and functional roles.

AccessNI clearance required

Please note, the successful candidate will be required to obtain AccessNI clearance prior to registration due to the nature of the project.

Essential criteria

Applicants should hold, or expect to obtain, a First or Upper Second Class Honours Degree in a subject relevant to the proposed area of study.

We may also consider applications from those who hold equivalent qualifications, for example, a Lower Second Class Honours Degree plus a Master’s Degree with Distinction.

In exceptional circumstances, the University may consider a portfolio of evidence from applicants who have appropriate professional experience which is equivalent to the learning outcomes of an Honours degree in lieu of academic qualifications.

• Sound understanding of subject area as evidenced by a comprehensive research proposal
• A comprehensive and articulate personal statement

Desirable Criteria

If the University receives a large number of applicants for the project, the following desirable criteria may be applied to shortlist applicants for interview.

• First Class Honours (1st) Degree
• Completion of Masters at a level equivalent to commendation or distinction at Ulster
• Practice-based research experience and/or dissemination
• Experience using research methods or other approaches relevant to the subject domain
• Work experience relevant to the proposed project
• Publications record appropriate to career stage
• Experience of presentation of research findings

Equal Opportunities

The University is an equal opportunities employer and welcomes applicants from all sections of the community, particularly from those with disabilities.

Appointment will be made on merit.

Funding and eligibility