Title

Study of the importance of broad sampling through NMR chemical-shift-based reweighting of intrinsically disordered proteins

Alternative Title

NMR chemical shift 기반 재가중을 통한 무정형 단백질의 광범위한 구조 탐색 중요성 연구

DGIST Authors

Juhyeong Jeon ; Wookyung Yu ; Jin Hae Kim

Advisor

유우경

Co-Advisor(s)

Jin Hae Kim

Issued Date

2026

Awarded Date

2026-08-01

Type

Thesis

Description

intrinsically disordered protein, conformational ensemble, NMR chemical shift, reweighting

Table Of Contents

Ⅰ.Introduction 1
1.1 Intrinsically Disordered Proteins and Protein Regions 1
1.2 Experimental and Computational Challenges in IDP Ensemble Characterization 1
1.3 Integration Algorithms 3
1.4 Multi-Prior Reweighting for Heterogeneous IDP Landscapes 4
1.5 NMR Chemical Shifts as a Reweighting Observable 4
1.6 Aim and Objectives 5
Ⅱ.Materials and Methods 6
2.1 Data Preprocessing 6
2.2 Ensemble Generation 7
2.3 Forward Model for Chemical Shift 8
2.4 Constrained Multiple Linear Regression 9
2.5 Maximum Entropy Reweighting Approach 10
2.6 Metrics 11
2.7 Offset Correction 12
2.8 Structural Analysis 14
Ⅲ.Results 16
3.1 Overall Workflow 16
3.1.1 Alignment and Filtering 17
3.1.2 Ensemble Generation and All-Atom Reconstruction 21
3.1.3 Chemical Shift Prediction 25
3.1.4 Parameter Selection and Metrics for Reweighting 28
3.1.5 Offset Correction 33
3.1.6 Outlier Removal and Final Reweighting 34
3.2 Effect of Ensemble Input 35
3.2.1 Atom Score Improvement 35
3.2.2 Dependence on the Number of Conformers 39
3.2.3 Relation between Score Improvement and Structural Features 42
3.3 Classification and Structural Analysis Based on Weights 48
3.3.1 Classification Criteria 48
3.3.2 Predictor Consistency of Classification 49
3.3.3 Information Content from Chemical Shift 52
3.3.4 Global Structural Features 56
3.3.5 AlphaFold Metrics across Classes 61
3.3.6 Model-Dependent Structural Biases 63
3.3.7 Model-Dependent Contributions to Statistical Weights 67
3.4 Case Studies of Reweighting 71
3.4.1 TDP-43: Mutation-Dependent Ensemble Redistribution 71
3.4.2 PHOX2B: Temperature-Dependent Ensemble Remodeling 75
Ⅳ.Discussion 81
Ⅴ.References 85
Appendix 94
Abstract in Korean 100

URI

https://scholar.dgist.ac.kr/handle/20.500.11750/60722
http://dgist.dcollection.net/common/orgView/200001006733

DOI

10.22677/THESIS.200001006733

Degree

Doctor

Department

Department of Brain Sciences

Publisher

DGIST

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