Summary of the report. Relationship between experimental and calculated characteristics
Our software can determine the range of changes in antibody affinity to antigen without additional experiments
Stabilization of amyloid peptides at the level of dimeric complexes
Purpose of the report. Determination of the physical parameters of the formation of amyloid biological complexes that cause their destabilization. This report proposes and describes in detail an original method for determining the stability and changes in the formation parameters of amyloid peptides dimers, as well as an analysis of the previously studied mutation (see Table 1)
Our method allows varying stability range of dimeric complexes by substitution of key amino acid residues, which are selected as shown in detail in this report. Numerical calculations will be presented in the form of a graphical representation, which clearly allows you to see an increase or decrease in the stability of dimeric, and, if necessary, tetrameric, hexameric, etc. amyloid
complexes.
Our method allows varying stability range of dimeric complexes by substitution of key amino acid residues, which are selected as shown in detail in this report. Numerical calculations will be presented in the form of a graphical representation, which clearly allows you to see an increase or decrease in the stability of dimeric, and, if necessary, tetrameric, hexameric, etc. amyloid
complexes.
Comparison of experimental [Dev Thacker,Kalyani Sanagavarapu,Birgitta Frohm,Georg Meisl, Tuomas P. J. Knowles, and Sara Linse. The role of fibril structure and surface hydrophobicity in secondary nucleation of amyloid fibrils
https://doi.org/10.1073/pnas.2002956117] and calculated values that characterize the stability of amyloid peptides and their ability to enter into biochemical processes (self‐aggregation) depending on the substitutions performed. The two upper graphs a) and b) were obtained from the experimental article [Dev Thacker,Kalyani Sanagavarapu,Birgitta Frohm,Georg Meisl, Tuomas P. J. Knowles, and Sara Linse. The role of fibril structure and surface hydrophobicity in secondary nucleation of amyloid fibrils// https://doi.org/10.1073/pnas.2002956117 ] at a concentration .1 μM. The time of half completion, t1/2, for the serine mutants in comparison with the WT Aβ42 in 20 mM sodium phosphate and 200 μM EDTA at pH 8.0 presented in the top two graphs. Below them are the corresponding calculated plots of the stability of dimeric complexes taking into account the substitutions d) and e). At the same time, for clarity of viewing and comparison, the reciprocal value 1 / lg (cond (W)) is given.
Thus, we see a relationship between the stability of dimeric modified amyloid peptides and the half‐life of their self‐aggregation. We explain it this way: the more stable the dimeric complex is, the slower it will enter into new biochemical processes. In this report, we focus on the peptide with four Serine substitutions, as it shows the least aggregation tendency, with the longest half‐life. The extreme graphs 2c) and 2f) are calculated. Graph 2c) shows the value of lg (cond (W)). The higher the value, the less stable the biological complex. The measure of the change in differential entropy is shown in Fig. 2f). This value is an additional parameter of control indicating the degree of order in the molecular system. If the character of the change in the value of ΔH coincides with the character of the change in the value of log (cond (W)), then there is no significant change in the conformation.
https://doi.org/10.1073/pnas.2002956117] and calculated values that characterize the stability of amyloid peptides and their ability to enter into biochemical processes (self‐aggregation) depending on the substitutions performed. The two upper graphs a) and b) were obtained from the experimental article [Dev Thacker,Kalyani Sanagavarapu,Birgitta Frohm,Georg Meisl, Tuomas P. J. Knowles, and Sara Linse. The role of fibril structure and surface hydrophobicity in secondary nucleation of amyloid fibrils// https://doi.org/10.1073/pnas.2002956117 ] at a concentration .1 μM. The time of half completion, t1/2, for the serine mutants in comparison with the WT Aβ42 in 20 mM sodium phosphate and 200 μM EDTA at pH 8.0 presented in the top two graphs. Below them are the corresponding calculated plots of the stability of dimeric complexes taking into account the substitutions d) and e). At the same time, for clarity of viewing and comparison, the reciprocal value 1 / lg (cond (W)) is given.
Thus, we see a relationship between the stability of dimeric modified amyloid peptides and the half‐life of their self‐aggregation. We explain it this way: the more stable the dimeric complex is, the slower it will enter into new biochemical processes. In this report, we focus on the peptide with four Serine substitutions, as it shows the least aggregation tendency, with the longest half‐life. The extreme graphs 2c) and 2f) are calculated. Graph 2c) shows the value of lg (cond (W)). The higher the value, the less stable the biological complex. The measure of the change in differential entropy is shown in Fig. 2f). This value is an additional parameter of control indicating the degree of order in the molecular system. If the character of the change in the value of ΔH coincides with the character of the change in the value of log (cond (W)), then there is no significant change in the conformation.
