Loading...
Publication
Analysis of residue interaction networks in molecular dynamics simulations
| Name: | Description: | Size: | Format: | |
|---|---|---|---|---|
| 3.35 MB | Adobe PDF |
Authors
Advisor(s)
Abstract(s)
É sabido que a estrutura de uma proteína não é estática, mas sim dinâmica. Porém, a análise
dinâmica da sua estrutura não é de todo fácil, muito por via das dimensões dos sistemas a
analisar. Por outro lado, a variedade de fatores que pode causar perturbações num sistema
biológico também dificulta a análise. Nesse sentido, as simulações de dinâmica molecular
(MD) apresentam-se como uma ferramenta muito importante pois geram toda uma biblioteca
de dados a partir de uma determinada simulação. A análise detalhada destes dados é um
processo complexo e demorado que requer diversas ferramentas computacionais.
Neste projeto foi utilizado a MDAnalysis, uma biblioteca open source orientada a objetos para
análise estrutural e temporal de resultados de dinâmica molecular, em particular de trajetórias
de simulação e de estruturas de proteínas. Está escrita na linguagem Python, com algum
código de desempenho crítico em C, recorrendo ainda a funcionalidades do pacote NumPy.
Adicionalmente, foi criado um script em Python que tentou facilitar e otimizar o processo com
via a obter uma interface que permita ao utilizador selecionar o tipo interações a analisar,
necessitando apenas de fornecer como input os ficheiros gro e xtc da dinâmica molecular de
uma simulação de sistema biológico. O script criado, por sua vez, faz todo o processo de
seleção, tratamento, análise e representação dos resultados com maior interesse da
simulação fornecida sobre a forma de ficheiro .pdf, bem como em formato .csv com os dados
detalhados da análise de cada simulação.
O script desenvolvido foi aplicado ao estudo da capacidade da transferrina, uma proteína
envolvida no transporte de ferro, associado ao anião carbonato, transportar também vanádio.
Foram analisadas as ligações para todos os tipos de interações possíveis envolvendo os
metais Fe(III) e V(III) e o anião sinergístico carbonato, nos diferentes estados de protonação
possíveis, de modo a validar o funcionamento do código desenvolvido.
Foi observado que as conformações mais fechadas da proteína estabelecem mais interacções
do que a conformação aberta, sendo a distância média na conformação fechada inferior à na
conformação relaxada. O anião favorecido através da análise das interações entre os metais
e os aniões para todas as proteínas, revelou ser o ácido carbónico, juntamente com o Fe(III)
uma vez que este estabelece mais interações do que V(III). Estes resultados correspondem
ao que é conhecido da literatura par esta proteína, permitindo validar o funcionamento do
código desenvolvido. Estes resultados permitem concluir que o código origina resultados
fiáveis.
It is known that the structure of the protein is not static, but its analysis is not at all easy, due to the dimensions of the studies, the variety of factors that can cause disturbances in a biological system also make these analyzes difficult. In this sense, molecular dynamics (MD) simulations are a very important tool because they generate a whole library of data from a given simulation. Uhis is a complex and time-consuming process that requires several computational tools to perform a detailed analysis. MDAnalysis was used in this project, it's an open source object-oriented library for structural and temporal analysis of molecular dynamics (MD), simulation's trajectories and structures analysis of individual proteins. It's written in Python language with some critical code in C, it also uses features from the NumPy package. Additionally, a python script was created in order to improve and optimize the process with an interactive user interface that would allow selecting the type of interactions to be analyzed, only needing to provide the .gro and .xtc files of the molecular dynamics of a molecular dynamics simulation as input. The script created makes the entire process of selection, treatment, analysis and representation easier. The results are provided in the form of .pdf as well as .csv. The developed script was applied to the study of the ability of transferrin, a protein involved in the transport of iron, associated with the carbonate anion, to also transport vanadium, as well as its ability to use other synergistic anions. Interactions were analyzed for all types of possible interactions involving metals - Fe(III) and V(III) - and the different protonation states of carbonate, in order to validate the script. It was observed that the closed and relaxed conformations of the protein were more likely to establish bonds than the open conformation. When there were coincident interactions, the average distance in the more closed conformation values were inferior to those of the relaxed conformation. The favored anion through the analysis of interactions between metals and anions for all proteins turned out to be carbonic acid, together with Fe(III) since this establishes more interactions than V(III). Additionally, in the case of the open conformation, interactions with cysteine residues were observed, although average values of distance of interactions are very high. These results indicate that the developed code is working as expected.
It is known that the structure of the protein is not static, but its analysis is not at all easy, due to the dimensions of the studies, the variety of factors that can cause disturbances in a biological system also make these analyzes difficult. In this sense, molecular dynamics (MD) simulations are a very important tool because they generate a whole library of data from a given simulation. Uhis is a complex and time-consuming process that requires several computational tools to perform a detailed analysis. MDAnalysis was used in this project, it's an open source object-oriented library for structural and temporal analysis of molecular dynamics (MD), simulation's trajectories and structures analysis of individual proteins. It's written in Python language with some critical code in C, it also uses features from the NumPy package. Additionally, a python script was created in order to improve and optimize the process with an interactive user interface that would allow selecting the type of interactions to be analyzed, only needing to provide the .gro and .xtc files of the molecular dynamics of a molecular dynamics simulation as input. The script created makes the entire process of selection, treatment, analysis and representation easier. The results are provided in the form of .pdf as well as .csv. The developed script was applied to the study of the ability of transferrin, a protein involved in the transport of iron, associated with the carbonate anion, to also transport vanadium, as well as its ability to use other synergistic anions. Interactions were analyzed for all types of possible interactions involving metals - Fe(III) and V(III) - and the different protonation states of carbonate, in order to validate the script. It was observed that the closed and relaxed conformations of the protein were more likely to establish bonds than the open conformation. When there were coincident interactions, the average distance in the more closed conformation values were inferior to those of the relaxed conformation. The favored anion through the analysis of interactions between metals and anions for all proteins turned out to be carbonic acid, together with Fe(III) since this establishes more interactions than V(III). Additionally, in the case of the open conformation, interactions with cysteine residues were observed, although average values of distance of interactions are very high. These results indicate that the developed code is working as expected.
Description
Keywords
Dinâmica Molecular POO - Programação Orientada a Objetos Python Redes de interação de aminoácidos MDAnalysis Molecular Dynamics Object-oriented Programming Aminoacid interaction networks