scholarly journals NMR as a Unique Tool in Assessment and Complex Determination of Weak Protein–Protein Interactions

2011 ◽  
pp. 35-45 ◽  
Author(s):  
Olga Vinogradova ◽  
Jun Qin
Keyword(s):  
Protein Interactions ◽  
Protein Protein Interactions

scholarly journals Structural design principles for specific ultra-high affinity interactions between colicins/pyocins and immunity proteins

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Avital Shushan ◽  
Mickey Kosloff
Keyword(s):  
Protein Interactions ◽  
Structural Elements ◽  
Protein Protein Interactions ◽  
Immunity Protein ◽  
Rational Engineering ◽  
High Affinity ◽  
Comparative Structure ◽  
Polar Interactions ◽  
Exquisite Specificity

AbstractThe interactions of the antibiotic proteins colicins/pyocins with immunity proteins is a seminal model system for studying protein–protein interactions and specificity. Yet, a precise and quantitative determination of which structural elements and residues determine their binding affinity and specificity is still lacking. Here, we used comparative structure-based energy calculations to map residues that substantially contribute to interactions across native and engineered complexes of colicins/pyocins and immunity proteins. We show that the immunity protein α1–α2 motif is a unique structurally-dissimilar element that restricts interaction specificity towards all colicins/pyocins, in both engineered and native complexes. This motif combines with a diverse and extensive array of electrostatic/polar interactions that enable the exquisite specificity that characterizes these interactions while achieving ultra-high affinity. Surprisingly, the divergence of these contributing colicin residues is reciprocal to residue conservation in immunity proteins. The structurally-dissimilar immunity protein α1–α2 motif is recognized by divergent colicins similarly, while the conserved immunity protein α3 helix interacts with diverse colicin residues. Electrostatics thus plays a key role in setting interaction specificity across all colicins and immunity proteins. Our analysis and resulting residue-level maps illuminate the molecular basis for these protein–protein interactions, with implications for drug development and rational engineering of these interfaces.

In silico specificity determination of neoantigen-reactive T-lymphocytes

2021 ◽  
Vol 67 (3) ◽  
pp. 251-258
Author(s):  
A.E. Kniga ◽  
I.V. Polyakov ◽  
A.V. Nemukhin
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Molecular Docking ◽  
Protein Interactions ◽  
Structural Features ◽  
Immune Recognition ◽  
Protein Protein Interactions ◽  
Binary Classifiers

Effective personalized immunotherapies of the future will need to capture not only the peculiarities of the patient’s tumor but also of his immune response to it. In this study, using results of in vitro high-throughput specificity assays, and combining comparative models of pMHCs and TCRs using molecular docking, we have constructed all-atom models for the putative complexes of all their possible pairwise TCR-pMHC combinations. For the models obtained we have calculated a dataset of physics-based scores and have trained binary classifiers that perform better compared to their solely sequence-based counterparts. These structure-based classifiers pinpoint the most prominent energetic terms and structural features characterizing the type of protein-protein interactions that underlies the immune recognition of tumors by T cells.

Determination of Protein–Protein Interactions in a Mixture of Two Monoclonal Antibodies

2019 ◽  
Vol 16 (12) ◽  
pp. 4775-4786 ◽  
Author(s):  
Priyanka Singh ◽  
Aisling Roche ◽  
Christopher F. van der Walle ◽  
Shahid Uddin ◽  
Jiali Du ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Protein Interactions ◽  
Protein Protein Interactions

Address of the President Lord Todd at the anniversary meeting, 30 November 1976

1977 ◽  
Vol 352 (1671) ◽  
pp. 451-462
Keyword(s):  
Protein Interactions ◽  
Complex Analysis ◽  
Organic Molecules ◽  
Heavy Atom ◽  
Vitamin B ◽  
Protein Protein Interactions ◽  
X Ray Crystallography ◽  
Polypeptide Chains ◽  
Complex Organic

The Copley Medal is awarded to Professor Dorothy M. C. Hodgkin, O. M., F. R. S. Professor Dorothy Hodgkin is distinguished for her research on the structure of complex organic molecules by the method of X-ray crystallography. She was among the first to appreciate the importance of heavy-atom phase-determining methods and these she used to effect the first complete determination of the stereochemistry of a sterol derivative in her analysis of cholesteryl iodide. The same powerful method of analysis and in particular her extraordinary gift of being able to interpret correctly the complex, partially resolved and often misleading electron density patterns that are first obtained, have been responsible for her success in elucidating the structures of many other important natural products, especially penicillin and vitamin B 12 . This last is by far the most beautiful and complex analysis which has yet been completed in this field and it is of fundamental importance to chemical science. In recent years Professor Hodgkin’s main interest has been devoted to the structure of insulin, on which she has been working on and off since 1935. Carried out with characteristic precision, this work has become a mine of stereochemical information relating to contacts between polypeptide chains and is of great significance for our interpretation of protein-protein interactions.

NMR for the design of functional mimetics of protein-protein interactions: one key is in the building of bridges

1998 ◽  
Vol 76 (2-3) ◽  
pp. 177-188 ◽  
Author(s):  
Jianxing Song ◽  
Feng Ni
Keyword(s):  
Protein Interactions ◽  
Binding Sites ◽  
Experimental Approach ◽  
Structural Information ◽  
Peptide Ligands ◽  
Protein Protein Interactions ◽  
Binding Residues ◽  
Related Proteins ◽  
Binding Inhibitors

Using the design of bivalent and bridge-binding inhibitors of thrombin as an example, we review an NMR-based experimental approach for the design of functional mimetics of protein-protein interactions. The strategy includes: (i) identification of binding residues in peptide ligands by differential resonance perturbation, (ii) determination of protein-bound structures of peptide ligands by use of transferred NOEs, (iii) minimization of larger protein and peptide ligands on the basis of NMR structural information, and (iv) linkage of two weakly binding mimetics to produce an inhibitor with enhanced affinity and specificity. This approach can be especially effective for the design of potent and selective functional mimetics of protein-protein interactions because it is less likely that the surfaces of two related proteins or enzymes share two identical binding sites or regions.Key words: NMR, protein-protein interactions, functional mimetics, bridge-binding inhibitors, thrombin.

Determination of Protein-Protein Interactions of ICln by the Yeast Two-Hybrid System

2001 ◽  
Vol 11 (1) ◽  
pp. 55-60 ◽  
Author(s):  
Andreas Schmarda ◽  
Friedrich Fresser ◽  
Martin Gschwentner ◽  
Johannes Fürst ◽  
Markus Ritter ◽  
...  
Keyword(s):  
Hybrid System ◽  
Protein Interactions ◽  
Protein Protein Interactions ◽  
Yeast Two Hybrid ◽  
Yeast Two Hybrid System ◽  
Two Hybrid

Experimental Methods for Determination of Protein–Protein Interactions

2021 ◽  
pp. 197-264
Author(s):  
Krishna Mohan Poluri ◽  
Khushboo Gulati ◽  
Sharanya Sarkar
Keyword(s):  
Protein Interactions ◽  
Experimental Methods ◽  
Protein Protein Interactions

Address of the President Lord Todd at the Anniversary Meeting, 30 November 1976

1977 ◽  
Vol 196 (1122) ◽  
pp. 1-12
Keyword(s):  
Protein Interactions ◽  
Complex Analysis ◽  
Organic Molecules ◽  
Heavy Atom ◽  
Vitamin B ◽  
Protein Protein Interactions ◽  
X Ray Crystallography ◽  
Polypeptide Chains ◽  
Complex Organic

The Copley Medal is awarded to Professor Dorothy M. C. Hodgkin, O. M., F. R. S. Professor Dorothy Hodgkin is distinguished for her research on the structure of complex organic molecules by the method of X-ray crystallography. She was among the first to appreciate the importance of heavy-atom phase-determining methods and these she used to effect the first complete determination of the stereochemistry of a sterol derivative in her analysis of cholesteryl iodide. The same powerful method of analysis and in particular her extraordinary gift of being able to interpret correctly the complex, partially resolved and often misleading electron density patterns that are first obtained, have been responsible for her success in elucidating the structures of many other important natural products, especially penicillin and vitamin B 12 . This last is by far the most beautiful and complex analysis which has yet been completed in this field and it is of fundamental importance to chemical science. In recent years Professor Hodgkin’s main interest has been devoted to the structure of insulin, on which she has been working on and off since 1935. Carried out with characteristic precision, this work has become a mine of stereochemical information relating to contacts between polypeptide chains and is of great significance for our interpretation of protein-protein interactions.

The result of equilibrium-constant calculations strongly depends on the evaluation method used and on the type of experimental errors

2001 ◽  
Vol 359 (2) ◽  
pp. 411-418 ◽  
Author(s):  
Hendrik FUCHS ◽  
Reinhard GESSNER
Keyword(s):  
Protein Interactions ◽  
Evaluation Method ◽  
Equilibrium Constants ◽  
Scatchard Analysis ◽  
Protein Protein Interactions ◽  
Data Set ◽  
Slow Kinetics ◽  
Experimental Errors ◽  
Saturation Effects

The determination of equilibrium constants is a widespread tool both to understand and to characterize protein–protein interactions. A variety of different methods, among them Scatchard analysis, is used to calculate these constants. Although more than 1000 articles dealing with equilibrium constants are published every year, the effects of experimental errors on the results are often disregarded when interpreting the data. In the present study we theoretically analysed the effect of various types of experimental errors on equilibrium constants derived by three different methods. A computer simulation clearly showed that certain experimental errors, namely inaccurate background correction, inexact calibration, saturation effects, slow kinetics and simple scattering, can adversely affect the result. The analysis further revealed that, for a given type of error, the same data set can produce different results depending on the method used.

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