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DERIVATION OF A REWEIGHTING ALGORITHM FOR THE PREDICTION OF THE THERMODYNAMIC STABILITY OF MUTATED SEQUENCES AND EVALUATION OF ITS USABILITY IN A SIMPLE CONTINUOUS PROTEIN MODEL

Henning, Frieder LU (2015) FYTK01 20142
Computational Biology and Biological Physics
Theoretical Particle Physics
Department of Astronomy and Theoretical Physics
Abstract
In this thesis, a new reweighting algorithm for predicting the native conformations of amino acid sequences, consisting of 16 residues in a reduced representation continuous protein model, is derived and tested to map neutral nets of α-helices and β-sheets.

For examining the potential of the reweighting algorithm for predicting the thermodynamic stability of amino acid sequences, it is applied to a mutational pathway, connecting a α-helix to a β-sheet. Moreover, a bistable sequence is used to predict the evolution of the chain properties along the pathway. The reweighted averages of four relevant observables are then compared to the averages obtained in direct simulations. Further, neutral nets of α-helices and β-sheets are mapped by... (More)
In this thesis, a new reweighting algorithm for predicting the native conformations of amino acid sequences, consisting of 16 residues in a reduced representation continuous protein model, is derived and tested to map neutral nets of α-helices and β-sheets.

For examining the potential of the reweighting algorithm for predicting the thermodynamic stability of amino acid sequences, it is applied to a mutational pathway, connecting a α-helix to a β-sheet. Moreover, a bistable sequence is used to predict the evolution of the chain properties along the pathway. The reweighted averages of four relevant observables are then compared to the averages obtained in direct simulations. Further, neutral nets of α-helices and β-sheets are mapped by using the reweighting algorithm. The compositions of the neutral nets are analyzed and the validity of the mapping is tested, both, in direct simulations and the analysis of a few sequences.

The evaluation of the usability of the reweighting algorithm indicates, that, in principle, it is capable of predicting the stability of native conformations. Moreover, the test cases show that for this method, bistable sequences are the most appropriate starting point for making predictions of the stability of other sequences. In the analysis of the neutral nets, it is shown that the compositions of the nets display some realistic features. However, as it turns out, some sequences, that are identified as belonging to either of the two nets do not fulfill the requirements that define these nets. (Less)
Abstract (Swedish)
I denna uppsats härleds och testas en ny omviktningsalgoritm med vars hjälp det nativa tillståndet av aminosyresekvenser, bestående av 16 aminosyror, kan förutspås. Algoritmen används till att kartlägga de neutrala näten av α-helixes och β-sheets inom ett kontinuerligt proteinmodell.

För att undersöka omviktningsalgoritmens potential för att förutsäga den termodynamiska stabiliteten av olika aminosyresekvenser används denna på en mutationsväg som leder från en α-helix till en β-sheet. Därutöver används en bistabil sekvens för att förutspå evolutionen av kedjornas egenskaper utmed mutationsvägen. De omviktade genomsnitten av fyra relevanta observabler jämförs sedan med genomsnittsvärden som mättes i direkta simuleringar av kedjorna.... (More)
I denna uppsats härleds och testas en ny omviktningsalgoritm med vars hjälp det nativa tillståndet av aminosyresekvenser, bestående av 16 aminosyror, kan förutspås. Algoritmen används till att kartlägga de neutrala näten av α-helixes och β-sheets inom ett kontinuerligt proteinmodell.

För att undersöka omviktningsalgoritmens potential för att förutsäga den termodynamiska stabiliteten av olika aminosyresekvenser används denna på en mutationsväg som leder från en α-helix till en β-sheet. Därutöver används en bistabil sekvens för att förutspå evolutionen av kedjornas egenskaper utmed mutationsvägen. De omviktade genomsnitten av fyra relevanta observabler jämförs sedan med genomsnittsvärden som mättes i direkta simuleringar av kedjorna. Sedan karläggs de neutrala näten av α-helixes och β-sheets med hjälp av omviktningsalgoritmen. De neutrala nätens komposition analyseras och deras giltighet testas både i direkta simuleringar och analysen av sammansättningen av ett antal aminosyresekvenser.

Undersökningen av omviktningsalgoritmens användbarhet antyder att algoritmen i princip är i stånd till att förutspå stabiliteten av proteiners nativa tillstånd. Därutöver visar testfallen att simuleringar av bistabila sekvenser är den lämpligaste utgångspunkt för att förutsäga stabiliteten av andra sekvenser. I analysen av de neutrala näten visas att nätens komposition är som väntad i vissa avseenden. Trots detta framgår det i en mera ingående undersökning att en del sekvenser som identifierades som tillhörande till ett av näten inte uppfyller kraven som definierar dessa. (Less)
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author
Henning, Frieder LU
supervisor
organization
course
FYTK01 20142
year
type
M2 - Bachelor Degree
subject
language
English
id
7616080
date added to LUP
2015-08-15 20:48:42
date last changed
2015-09-08 15:54:40
@misc{7616080,
  abstract     = {In this thesis, a new reweighting algorithm for predicting the native conformations of amino acid sequences, consisting of 16 residues in a reduced representation continuous protein model, is derived and tested to map neutral nets of α-helices and β-sheets.

For examining the potential of the reweighting algorithm for predicting the thermodynamic stability of amino acid sequences, it is applied to a mutational pathway, connecting a α-helix to a β-sheet. Moreover, a bistable sequence is used to predict the evolution of the chain properties along the pathway. The reweighted averages of four relevant observables are then compared to the averages obtained in direct simulations. Further, neutral nets of α-helices and β-sheets are mapped by using the reweighting algorithm. The compositions of the neutral nets are analyzed and the validity of the mapping is tested, both, in direct simulations and the analysis of a few sequences.

The evaluation of the usability of the reweighting algorithm indicates, that, in principle, it is capable of predicting the stability of native conformations. Moreover, the test cases show that for this method, bistable sequences are the most appropriate starting point for making predictions of the stability of other sequences. In the analysis of the neutral nets, it is shown that the compositions of the nets display some realistic features. However, as it turns out, some sequences, that are identified as belonging to either of the two nets do not fulfill the requirements that define these nets.},
  author       = {Henning, Frieder},
  language     = {eng},
  note         = {Student Paper},
  title        = {DERIVATION OF A REWEIGHTING ALGORITHM FOR THE PREDICTION OF THE THERMODYNAMIC STABILITY OF MUTATED SEQUENCES AND EVALUATION OF ITS USABILITY IN A SIMPLE CONTINUOUS PROTEIN MODEL},
  year         = {2015},
}