Projects – RESOLV

Name PIProject titleAbstractPublications
ChandanDasLars Schäfer, RUBMarked Structural Dynamics of the Active Site Protein-Water Network in the Prototypical Rigid Enzyme Human Carbonic Anhydrase II
Water molecules buried in protein active sites often govern their structure and dynamics. X-ray crystallography are widely used to locate such buried water molecules, whereas NMR can provide insights into the dynamical picture of coupled motions of water molecule(s) and the protein matrix. However, the interpretation of such NMR dynamics data in terms of the underlying atomic motions is often challenging, and assumptions and simplified motional models have to be invoked. MD simulations can aid the interpretation of such NMR experiments at the atomic level. Recent NMR experiments reported pronounced microsecond timescale conformational dynamics of the active site of apo HCAII, a text-book example for a prototypical rigid enzyme. HCAII regulates CO2/HCO¬¬3- interconversion and is a potential pharmacological target. The NMR particularly pointed to Thr198 located in an active site loop and, putatively, the highly conserved active site water network as showing marked conformational dynamics. Interestingly, this conformational dynamics was completely abrogated upon binding of a sulfonamide inhibitor. Our all-atom MD simulations visualize how the active site pocket is shaped by pronounced open/close conformational‐exchange dynamics of the Thr198-bearing loop and associated active site water molecules, which are strongly rigidified upon inhibitor binding.

Singh, H., Das, C.K., Vasa, S.K., Grohe, K., Schäfer, L.V., and Linser, R. (2020). The Active Site of a Prototypical “Rigid” Drug Target is Marked by Extensive Conformational Dynamics. Angew Chem Int Ed 59, 22916-22921. (10.1002/anie.202009348)
Singh, H., Vasa, S.K., Jangra, H., Rovó, P., Päslack, C., Das, C.K., Zipse, H., Schäfer, L.V., and Linser, R. (2019). Fast Microsecond Dynamics of the Protein–Water Network in the Active Site of Human Carbonic Anhydrase II Studied by Solid-State NMR Spectroscopy. J Am Chem Soc 141, 19276-19288. (10.1021/jacs.9b05311)
BanshiDasDominik Marx, RUBTowards Theoretical THz-VSFG Spectroscopy of Aqueous Interfaces and Nano-Confined Water
We aim to decipher the properties of nanoconfined water using the well known vibrational sum frequency generation (VSFG) technique. Unlike interfacial water, nanoconfined water has not yet been explored using VSFG technique, as most of the nanoconfinement set up, provides symmetric environment to the confined water, are unable to produce VSFG signal. Here we have modeled an asymmetric environment by taking graphene (GRA) on one side and boron nitride sheet (BNS) on the other side. With the use of external pressure on the rigid piston, we have simulated both the asymmetric (GRA-BNS) and symmetric (GRA-GRA) nanoconfinement and calculated the resonant part of the VSFG response.
GinnyKarirWolfram Sander, RUBPhotochemistry of BN Indoles in Cryogenic Matrices
DenizhanKesimClara Saraceno, RUBHigh repetition rate ultra-broadband THz sources based on plasma filaments
Currently, two-color THz generation in air and gas filaments has only been thoroughly explored at repetition rates <1kHz, mostly due to restrictions in the average power of ultrafast laser systems with sufficiently high pulse energies. In this project, we aim to access a regime of broadband, high-repetition rate, and strong-field THz sources so far inaccessible from laboratory-based setups, which would enable us to extend current solvation spectroscopy techniques to nonlinear regime. In this goal, we will develop a novel type of high-energy femtosecond laser system which should provide the necessary platform and explore two-color THz generation at high repetition rates.
CeliaMillonClara Saraceno, RUBFilamentation in water for efficient generation of broadband and mid-IR radiation
Until recently, the study of water in the THz frequency range has been considered impossible due to its large absorption. In this project, we investigate the direct measurement of THz transmission through a ~30-µm water-jet thickness which leads to an evaluation of the nonlinear refractive index of water in the range of 0.5 and 1.5 THz. A THz-Time Domain Spectroscopy (THz-TDS) setup using a LiNbO3 crystal pumped by a Ti:Sa generates THz-power up to 500 µW. So far, we have observed, through this experiment, different regimes of transmission in the frequency range of interest in accordance with recent studies.
SanjibMukherjeeRoland Winter, TUDUnveiling the conformational dynamics of multi-domain proteins at cell-like crowding and cosolvent conditions
The intrinsically disordered protein α-synuclein causes Parkinson’s disease by forming toxic oligomeric aggregates inside neurons, which can significantly impair DNA replication and transcription. Single-molecule Förster resonance energy transfer experiments are performed which provide mechanistic information about the interaction between the toxic oligomers and DNA at cell-mimicking conditions that are otherwise averaged out in ensemble-based experiments. Apart from measurements at various cosolute and crowding conditions, pressure-dependent experiments are carried out. They are of great importance in terms of biological relevance, but also from a physical-chemical point of view as they provide additional details about the free-energy landscape of the biomolecular system.

Knop, J.-M., Mukherjee, S.K., Oliva, R., Möbitz, S., and Winter, R. (2020). Remodeling of the Conformational Dynamics of Noncanonical DNA Structures by Monomeric and Aggregated α-Synuclein. J Am Chem Soc 142, 18299-18303. (10.1021/jacs.0c07192)
Oliva, R., Jahmidi-Azizi, N., Mukherjee, S., and Winter, R. (2021). Harnessing Pressure Modulation for Exploring Ligand Binding Reactions in Cosolvent Solutions. J Phys Chem B 125, 539-546. (10.1021/acs.jpcb.0c10212)
DavidOlivenza LeonKarina Morgenstern, RUBReal-space study of ion solvation
Femtosecond laser illumination has been used successfully to study the basic principles behind the reactions taking place on metallic interfaces. We suggest going a step further by investigating these reactions from a local point of view with the help of both a pump-probe ultrashort (50-100 fs) laser system and low-temperature scanning tunnelling microscopy (STM). This approach will be exemplified through the photodissociation processes analysed by means of two-photon photoelectron (2PPE) spectroscopy. First, we will study how two alkali ions of large relative size interact with both planar and non-planar solvents when the solvent is grown on a Cu(111) metallic substrate and which structures these ion-solvent complexes form. With this we want to gain knowledge on the influence of a cation mixture on solvent structure. Afterwards, we will use the pump-probe laser system to manipulate these ion-solvent complexes through photolytic dissociation while aiming to follow the reaction with a high temporal resolution (50-100 fs). With this project we expect to shed light on the influence of the ionic interactions and structures during reactions taking place on metallic surfaces at the atomic level, knowledge that is of interest to fields like energy conversion and sensor technology.
PradeepPantElsa Sanchez, RUBSolvent regulation of biomolecular function: pH-induced conformational changes in hemoglobin and albumin
JayitaPatwariKarina Morgenstern/Uwe Bovensiepen, RUB/UDEIon-solvent dynamics at interfaces on microscopic, molecular length and time scales
Ion-solvent interaction and electron transfer across hybrid interfaces are the key factors for energy storage and energy conversion applications. In this project, we investigate simple solvatomers on single-crystal metal surfaces which consist our of ions with coadsorbed solvents. We combine scanning tunneling microscopy and femtosecond time-resolved spectroscopy to obtain complementary insights regarding the solvatomer structure and electron dynamics, respectively. The goal is to distinguish the different solvation coordinates specific for such surface systems in the molecular structure and dynamic response of the solvatomers at surfaces.
StefanPiontekPoul Petersen, RUBUltrafast Dynamics in Electrochemical Systems: NLO Leads Us to the Next Frontier
SasharyRamosMartina Havenith, RUBTHz calorimetry for mapping water around the protein structure of azurin
ErnestoSantoroChristian Merten, RUBA novel OTTLE VCD cell for chiral optically active redox ions
VCD spectroscopy is an established tool for the determination of the absolute configuration of chiral molecule. To extend the field of the study to redox-active chiral species, limited today by a lack of commercial availible cells for such VCD measurements, the aim of this project is to build a novel electrochemical IR cell that allows us to record VCD spectra of chiral compounds in different oxidation states. The new cell will be used to characterize chiral transition metal compounds of relevance in bioinorganic chemistry and the structure-determining role of solvent molecules.
MinlongTaoKarina Morgenstern, RUBInvestigating the primary hydration with a low-temperature STM
Elianevan DamMartina Havenith, RUBElectrolyte-electrode interactions: water's perspective
In the use of renewable energy, a major challenge is energy storage. This always involves electron-electrode transfer, and thus electrode-electrolyte interactions play a crucial role. Despite its major role in solvation and mobility of the involved ions, solvent interactions have not been experimentally addressed. Therefore, we aim to obtain a complete molecular picture of the role of the solvent during electrolyte-electrode interactions. Using two complementary techniques, terahertz spectroscopy and THz sum frequency generation spectroscopy, we focus on water molecules interacting at the electrolyte-electrode interface. This leads to new insights regarding ion solvation in electrochemical processes, a fundamental factor in electron-electrode transfer.
ZhenyuWangJörg Neugebauer, MPI-Eisenf.Using a novel DFT potentiostat approach to study the fundamental charge and electron transfer reactions at metal-electrolyte interfaces
A fundamental understanding of the reactions at electrochemical solid-liquid interfaces is important to address technological challenges in fields such as electro-catalysis, electrochemical energy storage, or aqueous corrosion. Using ab initio calculations under explicit consideration of the aqueous environment and applied bias we study metal/water interfaces, focusing on metal dissolution, one of the most fundamental electrochemical reaction involving charge transfer. We test the assumption that density functional theory calculations are better suited to describe electron transfer reactions at solid/liquid interfaces compared to Marcus theory, because they account for the polarizability of charge within an atom.