Mechanisms of biochemical reactions within crowded environments

The cell interior is a highly packed environment in which biological macromolecules evolve and function. This crowded media has effects in many biological processes such as protein-protein binding, gene regulation, and protein folding. Thus, biochemical reactions that take place in such crowded conditions differ from diluted test tube conditions, and a considerable effort has been invested in order to understand such differences. In this work, we combine different computationally tools to disentangle the effects of molecular crowding on biochemical processes. First, we propose a lattice model to study the implications of molecular crowding on enzymatic reactions. We provide a detailed picture of how crowding affects binding and unbinding events and how the separate effects of crowding on binding equilibrium act together. Then, we implement a lattice model to study the effects of molecular crowding on facilitated diffusion. We find that obstacles on the DNA impair facilitated diffusion. However, the extent of this effect depends on how dynamic obstacles are on the DNA. For the scenario in which crowders are only present in the bulk solution, we find that at some conditions presence of crowding agents can enhance specific-DNA binding. Finally, we make use of structure-based techniques to look at the impact of the presence of crowders on the folding a protein. We find that polymeric crowders have stronger effects on protein stability than spherical crowders. The strength of this effect increases as the polymeric crowders become longer. The methods we propose here are general and can also be applied to more complicated systems.

Level thesis:degree_level

thesis.doctoral

Grantor dc:publisher

Universität Potsdam

Year

2016

Author dc:creator

• Gomez, David

Contributors dc:contributor

• Klumpp, Stefan

• molecular crowding
• gene expression
• enzymatic activity
• protein folding
• enzymatische Reaktionen
• Genregulation
• Faltung von Proteinen

Statement dc:rights

• CC-BY-NC-SA - Namensnennung, nicht kommerziell, Weitergabe zu gleichen Bedingungen 4.0 International

Repository record source_url

https://publishup.uni-potsdam.de/frontdoor/index/index/docId/9459

OAI identifier oai:identifier

oai:kobv.de-opus4-uni-potsdam:9459