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FibSim, a web application to refine fibrillar macromolecular models

Burleigh, Stephen (2016) BINP30 20152
Degree Projects in Bioinformatics
Abstract
Fibrillar macromolecules are long, linear structures that have helical symmetry. A technique called X-ray fiber diffraction (XRFD) is often used to help solve the three-dimensional structure of fibrillar macromolecules. Models of fibrillar structure, built de novo, using homologs or using experimental data derived from other methods should be compared to this experimental XRFD data to test and refine the models. To facilitate this comparison, software has been developed to simulate XRFD data from fibrillar models, which is then compared to the experimental data. However, currently this process often involves a few independent programs. A new program has recently been developed that, in one package, generates simulated XRFD data from the... (More)
Fibrillar macromolecules are long, linear structures that have helical symmetry. A technique called X-ray fiber diffraction (XRFD) is often used to help solve the three-dimensional structure of fibrillar macromolecules. Models of fibrillar structure, built de novo, using homologs or using experimental data derived from other methods should be compared to this experimental XRFD data to test and refine the models. To facilitate this comparison, software has been developed to simulate XRFD data from fibrillar models, which is then compared to the experimental data. However, currently this process often involves a few independent programs. A new program has recently been developed that, in one package, generates simulated XRFD data from the model and compares it statistically to the experimental XFRD data, if included in the simulation. The outcome of the statistical test can then be used to guide the refinement of the model. This package also uses an algorithm that utilizes ‘simultaneous model building’ to improve predictions. Currently, this software is server-bound, computationally intensive and has minimalistic, command-line functionality. As a means to publically share this unique program, I present FibSim, a web server for this fibrillar refinement program. FibSim provides the model-refinement functionality of the original software with an easy-to-use graphical user interface. (Less)
Popular Abstract
A website to refine models of protein 3D structure

Knowing the three dimensional (3D) structure of biological molecules can help us understand their function within cells. One group of biomolecules, called fibrillar macromolecules, are made of small subunits that join together forming a helical structure similar to a shape of a spiraling staircase. This arrangement of subunits around a central core makes fibrillar macromolecules linear, extended and often tensely strong. One famous fibrillar protein macromolecule is collagen, a component of our skin and muscles. Thus, one can see the motivation behind studying these biomolecules- we may be able to one day manipulate their function for our benefit, but only after we gain a thorough... (More)
A website to refine models of protein 3D structure

Knowing the three dimensional (3D) structure of biological molecules can help us understand their function within cells. One group of biomolecules, called fibrillar macromolecules, are made of small subunits that join together forming a helical structure similar to a shape of a spiraling staircase. This arrangement of subunits around a central core makes fibrillar macromolecules linear, extended and often tensely strong. One famous fibrillar protein macromolecule is collagen, a component of our skin and muscles. Thus, one can see the motivation behind studying these biomolecules- we may be able to one day manipulate their function for our benefit, but only after we gain a thorough understanding of their structure.

Fibrillar macromolecules are often studied using a method called X-ray fiber diffraction, which provides vital information on both the subunit’s structure and helical nature of the protein complex. From this data 3D models can be made. The next step involves comparing these predicted models to experimental data in a process called refinement. This refinement process usually involves a number of computer programs, although recently one group has made a single program that refines fibrillar models and includes a statistical test to help guide the refinement process. However, their program is rather complex and uses considerable computing power, making it difficult to distribute as a single downloadable program.

The project
This project is the development a web server for providing public access to this new fibrillar refinement program. Presenting the program as a web site allows users access to the refinement functionality of the original program and allows the use of a powerful server that can speed calculations. We showed that the statistical test used to compare the model with experimental data could be used to step-wise improve the model. The site made use of a ‘web framework’ called Django, which helped provide basic website functions, such as an administrative page, a database, a contact page and the tools needed for users to download or email results.

Advisor: Ingemar André
Department of Biochemistry and Structural Biology, Lund University
Master´s Degree Project, 30 cr, in Bioinformatics, 2016
Department of Biology, Lund University (Less)
Please use this url to cite or link to this publication:
author
Burleigh, Stephen
supervisor
organization
course
BINP30 20152
year
type
H2 - Master's Degree (Two Years)
subject
language
English
id
8870647
date added to LUP
2016-04-04 11:42:42
date last changed
2016-04-04 11:42:42
@misc{8870647,
  abstract     = {Fibrillar macromolecules are long, linear structures that have helical symmetry. A technique called X-ray fiber diffraction (XRFD) is often used to help solve the three-dimensional structure of fibrillar macromolecules. Models of fibrillar structure, built de novo, using homologs or using experimental data derived from other methods should be compared to this experimental XRFD data to test and refine the models. To facilitate this comparison, software has been developed to simulate XRFD data from fibrillar models, which is then compared to the experimental data. However, currently this process often involves a few independent programs. A new program has recently been developed that, in one package, generates simulated XRFD data from the model and compares it statistically to the experimental XFRD data, if included in the simulation. The outcome of the statistical test can then be used to guide the refinement of the model. This package also uses an algorithm that utilizes ‘simultaneous model building’ to improve predictions. Currently, this software is server-bound, computationally intensive and has minimalistic, command-line functionality. As a means to publically share this unique program, I present FibSim, a web server for this fibrillar refinement program. FibSim provides the model-refinement functionality of the original software with an easy-to-use graphical user interface.},
  author       = {Burleigh, Stephen},
  language     = {eng},
  note         = {Student Paper},
  title        = {FibSim, a web application to refine fibrillar macromolecular models},
  year         = {2016},
}