Thema der Dissertation:
Vibrational and Scaling Cascades in Conformational Dynamics of (Alanine-Leucine)n-Peptides
Vibrational and Scaling Cascades in Conformational Dynamics of (Alanine-Leucine)n-Peptides
Abstract: Proteins are vital for life because they perform a wide variety of functions in living organisms. Being flexible and dynamic molecules, proteins inherit conformational diversity, a crucial element for their function in the aqueous environment. This structural heterogeneity and the synergy between non-covalent intramolecular interactions of proteins and protein-water interactions are considered the driving elements of such conformational transitions. Thus, the conformational dynamics of proteins, water fluctuations, and their coupling play a crucial role in many biological functions, such as ligand binding. Typically, protein or peptide dynamics take place at longer timescales, while the timescales of water dynamics are around picoseconds, mainly due to the high mobility of water molecules and frequent changes in the hydrogen bonding state.
Peptides are often used as small, tractable model systems for proteins to study their conformational dynamics and the dynamics of the surrounding water molecules. This thesis aims for understanding the scaling cascades in the vibrational and conformational dynamics of peptides, exemplified on the model (Ala-Leu)n-based peptides by utilizing classical and first-principles molecular dynamics (MD) simulations, Markov state modelling (MSM), and vibrational spectroscopy.
First, to interpret the measured IR spectrum of the small floppy peptide, Ala-Leu (AL), in terms of the possible responsible conformations and to investigate the precise conformational dynamics of the peptide, we developed a combined approach, i.e., classical MD simulations plus MSM’s and theoretical IR spectrum calculations. Using such an approach, the experimentally observed vibrational signatures of peptides/proteins can be assigned/dissected into spectra of their constituent metastable-conformers.
Second, the hydration shell of Ala-Leu-Ala-Leu (ALAL), particularly around the central carbonyl group (C2=O2), is analysed. The factors that influence the instantaneous vibrational frequency, and thus the observed spectroscopic signature in the Amide-I region, were inspected. The dynamics and topology of hydrating waters cannot be neglected. The hydrogen bond probabilities of carbonyl groups match the calculated stretching frequency shifts. The C2=O2 showed a clear trend of the red-shift in its vibrational frequencies with the averaged number of hydrogen-bonded water molecules. The amount of the (additional) red-shift is determined by the interaction of the second water molecule.
Third, the connection between the slow, functionally relevant metastable conformations of ALAL and the fast solvent dynamics/local atomic fluctuations is studied. The different water topology/dynamics of the different metastable conformations affect the vibrational strength of the individual polar bond differently, impacting the calculated composed IR spectrum of the peptide.
Lastly, the effect of change in the length of the (Ala-Leu)n peptide on the timescales of slow conformation transitions, hydration shell geometry and Amide-I spectra is studied.
Peptides are often used as small, tractable model systems for proteins to study their conformational dynamics and the dynamics of the surrounding water molecules. This thesis aims for understanding the scaling cascades in the vibrational and conformational dynamics of peptides, exemplified on the model (Ala-Leu)n-based peptides by utilizing classical and first-principles molecular dynamics (MD) simulations, Markov state modelling (MSM), and vibrational spectroscopy.
First, to interpret the measured IR spectrum of the small floppy peptide, Ala-Leu (AL), in terms of the possible responsible conformations and to investigate the precise conformational dynamics of the peptide, we developed a combined approach, i.e., classical MD simulations plus MSM’s and theoretical IR spectrum calculations. Using such an approach, the experimentally observed vibrational signatures of peptides/proteins can be assigned/dissected into spectra of their constituent metastable-conformers.
Second, the hydration shell of Ala-Leu-Ala-Leu (ALAL), particularly around the central carbonyl group (C2=O2), is analysed. The factors that influence the instantaneous vibrational frequency, and thus the observed spectroscopic signature in the Amide-I region, were inspected. The dynamics and topology of hydrating waters cannot be neglected. The hydrogen bond probabilities of carbonyl groups match the calculated stretching frequency shifts. The C2=O2 showed a clear trend of the red-shift in its vibrational frequencies with the averaged number of hydrogen-bonded water molecules. The amount of the (additional) red-shift is determined by the interaction of the second water molecule.
Third, the connection between the slow, functionally relevant metastable conformations of ALAL and the fast solvent dynamics/local atomic fluctuations is studied. The different water topology/dynamics of the different metastable conformations affect the vibrational strength of the individual polar bond differently, impacting the calculated composed IR spectrum of the peptide.
Lastly, the effect of change in the length of the (Ala-Leu)n peptide on the timescales of slow conformation transitions, hydration shell geometry and Amide-I spectra is studied.
Zeit & Ort
25.05.2022 | 16:00
Hörsaal A (1.3.14)
Fachbereich Physik, Arnimallee 14, 14195 Berlin