Development and application of new 1H-detected solid-state NMR methods to expand dimensionality and study protein-ligand interactions

Aug 26, 2026

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This dissertation investigates the development and application of new 1H-detected solid-state NMR methods aimed at expanding experimental dimensionality. It establishes approaches to analyze protein-ligand interactions with higher-dimensional experiments that support resonance assignments. The work emphasizes projection spectroscopy and related techniques, including automated projection spectroscopy and signal separating algorithms, alongside specific studies on model proteins and ligand-binding systems. Materials and methods document protein sample preparation and NMR pulse program usage.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages254

Reading Time10 h 40 min

AccessFree to download

Contents

Introduction

Projection spectroscopy in solid-state NMR

Higher-dimensional experiments for resonance assignments

Protein-ligand interactions

Discussion and outlook

Materials and Methods

Supplement

Dissertation zur Erlangung des Doktorgrades der Fakultät für Chemie und Pharmazieder Ludwig-Maximilians-Universität München Development and application of new 1 Hdetected solid-state NMR methods to expand dimensionality and study proteinligand interactions Alexander Klein aus Villingen-Schwenningen, Deutschland Erklärung Diese Dissertation wurde im Sinne von § 7 der Promotionsordnung vom 28. November 2011 von Herrn Prof. Dr. Rasmus Linser betreut. Eidesstattliche Versicherung Diese Dissertation wurde eigenständig und ohne unerlaubte Hilfe erarbeitet. München, 02.11.2021 Dissertation eingereicht am 1. Gutachter: 2. Gutachter: Mündliche Prüfung am Alexander Klein 10.11.2021 Prof. Dr. Rasmus Linser Prof. Dr. Henry Dube 21.12.2021 Acknowledgements The end of my Ph.D. marks the end of a journey in a literal and metaphorical sense, and I could not have completed this journey without the assistance of many persons along the way, to which I want to say ’Thank you!’. First, I want to thank Prof. Rasmus Linser for being my supervisor and teacher. He always motivated me and is an inspiring researcher that gave me many great ideas, of which some were not as "fast" as initially thought. When projects seemed to be stuck, he often gave the necessary leap forward and with that also fresh motivation. From the first interview, he created an open-minded environment both personally and scientifically that I did not take for granted. He was always willing to spend as much time as possible discussing the latest results or sit together at the spectrometers. I also want to express my gratitude for the many workshops and conferences I was allowed to visit worldwide. My second thank goes to Prof. Henry Dube for taking the role of being my second reviewer on short notice and unforeseen circumstances and to Prof. Konstantin Karaghiosoff, whom I wish all the best and fast recovery at this time. I found an excellent research atmosphere and a very welcoming environment in the group from the very beginning. Special thanks go to Dr. Suresh Vasa and Dr. Petra Rovó, who taught me many things about solid-state NMR, pulse programming, spectrometer hardware and were always open to discuss problems at any time. They contributed a lot to the direction this journey took. I want to thank Dr. Kristof Grohe and Dr. Diana Pöllmann for helping me to take the first steps with protein expression, and Sara Medina Gómez, Julia Kotschy, Dr. Laura Kukuk, and Dr. Himanshu Singh for ongoing assistance in this field. I also want to thank all the other fellow PhDs and PostDocs in the group or scientific family in Munich and Dortmund: Ekatarina Burakova, Benedikt Söldner, Romeo Dubini, Hanna Kavaleuskaya, and Dr. Elias Akoury, as well as Maria Sergani and Christine Wehbrink for administrative support. It has been a pleasure talking to you and discussing with you, having coffee breaks, and delicious international brunches. I want to thank my parents for encouraging me all the time beyond any doubt, for helping me move from one city to the other three times, and for guiding me my entire way. I would not have made it that far without their support. A special thank goes to Sara, who joined the group as a colleague and is now the wonderful partner at my side. She is there in times of doubt and constantly changes how I see myself in the best possible way. Last but not least, I want to acknowledge all the many other persons that I have encountered along the way, even though not mentioned, which all helped in one way or another to bring this journey to an end. Contents 1 Introduction 3 1.1 Physical principles in NMR spectroscopy . . . . . . . . . . . . . . . . . . . . . 4 1.2 Solid-state NMR . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 1.2.1 1H-detected solid-state NMR spectroscopy ................ 11 1.3 Basic concepts of relaxation in solution and solid-state NMR 1,2 ........ 13 1.4 Concepts of no

FAQs

What is the main goal of the dissertation?

To develop and apply new 1H-detected solid-state NMR methods that expand dimensionality and enable studies of protein-ligand interactions.

How does projection spectroscopy contribute to the work?

Projection spectroscopy, including automated projection spectroscopy (APSY) and signal separating algorithms, supports efficient higher-dimensional acquisition and processing.

Which protein systems are used to demonstrate the methods?

The dissertation studies several proteins as model systems, including the SH3 domain, tryptophan synthase, and human carbonic anhydrase II (hCAII) for protein-ligand interaction analyses.

Aug 26, 2026

Uploaded by Mia