Peripheral membrane protein simulations 2

Dnr:

SNIC 2017/1-188

Type:

SNAC Medium

Principal Investigator:

Erik Marklund

Affiliation:

Uppsala universitet

Start Date:

2017-04-20

End Date:

2017-11-01

Primary Classification:

10602: Biokemi och molekylärbiologi

Secondary Classification:

10610: Bioinformatik och systembiologi (metodutveckling under 10203)

Webpage:

http://www.kemi.uu.se/research/biochemistry/marklund-group/

Allocation

Abstract

Extension of project snic2017-7-15 The peripheral membrane protein DHODH has been identified as a potential drug target for cancer treatment, and is associated with several other illnesses and additionally suggested as a target for antibiotics development. In short, it is an enzyme that effectively regulates the transcription and replication machinery in response to the levels of available substrates for nucleotide production. Its role is often changed in cancer cells however, which provides an avenue to specifically target the latter. A number of inhibitors have been identified for DHODH, and there are several structures models available in the protein data bank. Mass-spectrometry experiments in an ongoing project have cast new light on the importance of lipid–protein interactions of DHODH for the binding of one well-known inhibitor. These experiments are "low-resolution" however, and there are a number of questions where molecular dynamics simulations would provide valuable insight into the details of ligand binding and function. Surprisingly, DHODH has not been studied in atomic detail in the presence of an actual membrane, and simulations would be able to charter some very fundamental features of this protein, which would be valuable for the design of new drugs for treatment of cancer and other diseases.