Novel applications for hierarchical natural move Monte Carlo simulations: from proteins to nucleic acids

Thesis

Biological molecules often undergo large structural changes to perform their function. Computational methods can provide a fine-grained description at the atomistic scale. Without sufficient approximations to accelerate the simulations, however, the time-scale on which functional motions often occur is out of reach for many traditional methods. Natural Move Monte Carlo belongs to a class of methods that were introduced to bridge this gap. I present three novel applications for Natural Move Monte Carlo, two on proteins and one on DNA epigenetics. In the second part of this thesis I introduce a new protocol for the testing of hypotheses regarding the functional motions of biological systems, named customised Natural Move Monte Carlo. Two different case studies are presented aimed at demonstrating the feasibility of customised Natural Move Monte Carlo.

Authors: Demharter, S

• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Keywords: Functional Motions; epigenetic marks; Hypothesis-testing
• Subjects: Molecular Simulations; Structural bioinformatics; Protein dynamics