Anomalous Diffusion in Protein Dynamics

by Andreas Volkhardt
Doctoral thesis
Date of Examination:2021-10-26
Date of issue:2022-02-14
Advisor:Prof. Dr. Helmut Grubmüller
Referee:Prof. Dr. Helmut Grubmüller
Referee:Prof. Dr. Jörg Enderlein
Persistent Address: http://dx.doi.org/10.53846/goediss-44

 

 

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Abstract

English

Almost all processes in life are governed by proteins which are biomolecules consisting of a chain of amino acids. They perform a wide range of functions in organisms, including catalysis of metabolic reactions, transport of molecules, transcription of DNA to RNA, and ensuring the structural stability of cells.This function is intimately linked to a proteins’ three-dimensional structure and its dynamics. Protein dynamics is a complex process comprised of motions on multiple orders of magnitude both in characteristic time-scale and amplitude. Frauenfelder et al. suggested that this complex process can be modeled as a diffusion process in a hierarchically structured free energy landscape. With the rapid improvement in performance of computer hardware protein dynamics can be simulated on multiple time scales. Indeed, it was found that protein dynamics shows anomalous diffusion which is a characteristic feature of diffusion processes in hierarchical free-energy landscapes. The main aim of this work is to investigate the hierarchical structure of protein free-energy landscapes. To that end, we use a d-dimensional generalization of the simple hierarchical lattice model as a reference to translate anomalous diffusion exponents obtained from MD simulations into ruggedness and dimensionality estimates. We were able to estimate the ruggedness and dimensionality estimates of 500 small globular proteins from one-microsecond molecular dynamics simulations based on this d-dimensional hierarchical lattice model. Furthermore, we asked what the cause of anomalous diffusion in hierarchical free energy landscapes is. Based on this, we developed an enhanced sampling algorithm for simulating diffusion in hierarchical free energy landscapes.
Keywords: Anomalous diffusion; Hierarchical free energy landscapes; Protein dynamics; Molecular dynamics
 
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