1. S PIN MODEL OF WATER AND POST- PROCESSING OF PROTEIN FOLDING EXPERIMENTSArtem Badasyan, Knarik Yeritsyan, 2023, objavljeni povzetek znanstvenega prispevka na konferenci Opis: The presence of several distinct minima in nearest-neighbor potentials in polymers makes it possible
to describe polymer conformations in terms of discrete isomeric states, naturally leading to spin
language. Using this general approach, a decade ago we have suggested the Hamiltonian formulation
for the Zimm and Bragg model of protein conformations [1,2]. Later we have augmented the model
by an oversimplified spin model for water, resulting in both cold and hot denaturations [3]. We
construct the Statistical Mechanics for the model and get access to its Thermodynamics. Resulting
order parameter and specific heat expressions are successfully fit to available experimental data [4].
Thanks to solid and traceable theoretical foundations, the procedure provides better quality fits as
compared to the state-of-the-art two-state model, routinely used to process protein folding
experiments. Ključne besede: SPIN MODEL, WATER, PROTEIN FOLDING Objavljeno v RUNG: 04.09.2023; Ogledov: 135; Prenosov: 1
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2. Potts spins, protein conformations and implicit water modelArtem Badasyan, 2023, objavljeni povzetek znanstvenega prispevka na konferenci (vabljeno predavanje) Opis: I will summarize past and current achievements in the field of spin model applications to protein conformations. Using classical Statistical Mechanics scheme and 1D many-body Hamiltonian, exact partition function can be estimated, giving access to the free energy, order parameter and specific heat. I will introduce a simplified water model as an additive term at the level of Hamiltonian, and will show how the solvent degrees of freedom can be summed out. The suggested procedure results in the effective Hamiltonian with the temperature dependent hydrogen bonding energy. If the many-body range is reduced to the nearest neighbour, the approach reduces to the Zimm-Bragg model. Obtained expressions for the order parameter and the specific heat nicely fit to the corresponding experiments for protein folding, providing an alternative or complementary scheme for the processing of experimental data. Ključne besede: protein folding, Zimm-Bragg, protein-water interactions Objavljeno v RUNG: 19.06.2023; Ogledov: 329; Prenosov: 2
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3. Spin Model of Protein Conformations in water: Theory vs Experiment.Artem Badasyan, Knarik Yeritsyan, objavljeni povzetek znanstvenega prispevka na konferenci (vabljeno predavanje) Opis: Background (approx. 70 words) I will overview the application of spin models of Statistical Mechanics to describe polypeptide conformations. Zimm and Bragg model is one of the most successful examples of such approach [1]. In 2010 we have suggested the microscopic formulation of the model [2], which was later augmented by including the interactions with water [3]. Adding the solvent opened doors for the direct comparisons with UV-vis, Circular Dichroism (CD) and Differential Scanning Calorimetry (DSC) experiments.
Aim (approx. 30 words) Based on a statistical Potts-like spin model of protein folding we provide formulas for experimentally measurable quantities and report a perfect fit. Our approach suggest a new method to process the results of protein folding experiments.
Method (approx. 100 words) We start from the microscopic Hamiltonian formulation of the polypeptide model in water and use the usual Statistical Mechanics route from the model to partition function and the thermodynamics. Using Mayer expansion and summation over the solvent degrees of freedom, the problem is shown to be equivalent to in vacuo model with some effective, temperature dependent interaction energy. Estimated partition function leads to the expressions for the thermodynamic potentials and order parameter averages. The comparison (least-square fit) with the experimental data points from CD and DSC experiments on protein folding allows to extract the information on hydrogen bonding strengths, not available with the classical approach.
Results & Discussion (approx 200 words, or less if you paste an image or insert a table )
Proposed model allows for the cold denaturation under certain well-defined conditions. The agreement between the theoretical curves and data points is excellent, and the values of fitted parameters are within the expected ranges. The limitations of the approach are naturally related to the limitations of the Zimm-Bragg original model, intended to describe the changes of the secondary structure elements only. Taking into account that the so-called “two-state” model widely used nowadays to process the experiment does not contain any info regarding the hydrogen bonding energies, the method we suggest provides a promising alternative.
Conclusion (70 words approximately)
The proposed approach does what it is intended to do: processing of the experimental data on protein folding. However the model contains the very same serious limitations, as the two-state model: it is oversimplified in many respects. Whether the currently available experimental methods need a better model than already suggested ones or not, is an open question.
References:
[1] Zimm, B.H.; Bragg, J.K.; J. Chem. Phys. 31:526–535 (1959).
[2] Badasyan, A.V. et al., Phys. Rev. E 81:021921 (2010).
[3] Badasyan, A.V. et al., Phys. Rev. E 89:022723 (2014).
[4] Badasyan, A. et al.; Eur.Phys. J. E 36:1–9 (2013). Ključne besede: Protein folding, CD, DSC, Zimm-Bragg Objavljeno v RUNG: 15.05.2023; Ogledov: 406; Prenosov: 0 Gradivo ima več datotek! Več... |
4. Protein quality control for improved data reproducibility and reliabilityKim Remans, Ario de Marco, Nick Berrow, Mario Lebendiker, Maria Garcia-Alai, Stefan Knauer, Andre Matagne, Anne Perret, Stephan Uebel, Bertrand Raynal, 2022, objavljeni povzetek znanstvenega prispevka na konferenci Ključne besede: protein quality, evaluation assays, biophysical methods Objavljeno v RUNG: 13.04.2023; Ogledov: 392; Prenosov: 0 Gradivo ima več datotek! Več... |
5. Design of nanobody-based bispecific constructs by in silico affinity maturation and umbrella sampling simulationsZixuan Bai, Jiewen Wang, Jiaqi Li, Haibin Yuan, Ping Wang, Miao Zhang, Yuanhang Feng, Xiangtong Cao, Xiangan Cao, Guangbo Kang, Ario de Marco, He Huang, 2023, izvirni znanstveni članek Ključne besede: nanobody rational design, bispecific binders, protein activity inhibition Objavljeno v RUNG: 03.01.2023; Ogledov: 521; Prenosov: 0 Gradivo ima več datotek! Več... |
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10. Protein purification strategies must consider downstream applications and individual biological characteristicsKim Remans, Mario Lebendiker, Celeste Abreu, Mariano Maffei, Shaila Sellathurai, Marina May, Ondrej Vanek, Ario de Marco, 2022, pregledni znanstveni članek Ključne besede: protein purification, quality control, protein functionality Objavljeno v RUNG: 08.04.2022; Ogledov: 1033; Prenosov: 189
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