Study of molecular processes through calculation of multidimensional free energy landscapes

Wojtas-Niziurski, Wojciech. Study of molecular processes through calculation of multidimensional free energy landscapes. 2014, Doctoral Thesis, University of Basel, Faculty of Science.


Official URL: http://edoc.unibas.ch/diss/DissB_11986

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The potential of mean force describing conformational changes of biomolecules is a central quantity for understanding the function of biomolecular systems. Calculating an energy landscape of a process that depends on three or more reaction coordinates requires extensive computational power, making some multi-dimensional calculations practically impossible. Here, I present an efficient automatized umbrella sampling strategy for calculating a multidimensional potential of mean force. The method progressively learns by itself, through a feedback mechanism, which regions of a multidimensional space are worth exploring and automatically generates a set of umbrella sampling windows that is adapted to the system. The self-learning adaptive umbrella sampling method is first explained with illustrative examples based on simplified reduced model systems and then applied to two nontrivial situations: the conformational equilibrium of the pentapeptide Met-enkephalin in solution and ion permeation in the KcsA potassium channel. With this method, it is demonstrated that a significant smaller number of umbrella windows needs to be employed to characterize the free energy landscape over the most relevant regions without any loss in accuracy.
Advisors:Schwede, Torsten and Bernèche, Simon and Dal Peraro, Matteo
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Computational & Systems Biology > Bioinformatics (Schwede)
UniBasel Contributors:Wojtas-Niziurski, Wojciech and Schwede, Torsten and Bernèche, Simon
Item Type:Thesis
Thesis Subtype:Doctoral Thesis
Thesis no:11986
Thesis status:Complete
Number of Pages:1 Online-Ressource (83 Seiten)
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edoc DOI:
Last Modified:22 Apr 2018 04:32
Deposited On:28 Dec 2016 10:36

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