Prediction of Protein-Protein Interaction Using Distance Frequency of Amino Acids Grouped with their Physicochemical Properties

2011 ◽  
Author(s):  
Shao-Wu Zhang ◽  
Yong-Mei Cheng ◽  
Li Luo ◽  
Quan Pan
Keyword(s):  
Amino Acids ◽  
Physicochemical Properties ◽  
Protein Interaction ◽  
Protein Protein Interaction

scholarly journals Quantitative Estimate of Protein-Protein Interaction Targeting Drug-likeness

2021 ◽  
Author(s):  
Takatsugu Kosugi ◽  
Masahito Ohue
Keyword(s):  
Physicochemical Properties ◽  
Protein Interaction ◽  
Quantitative Estimate ◽  
Early Stage ◽  
Assessment Method ◽  
Early Screening ◽  
Protein Protein Interaction ◽  
Approved Drugs ◽  
Fda Approved Drugs ◽  
Discriminatory Performance

The quantification of drug-likeness is very useful for screening drug candidates. The quantitative estimate of drug-likeness (QED) is the most commonly used quantitative drug efficacy assessment method proposed by Bickerton <i>et al</i>. However, QED is not considered suitable for screening compounds that target protein-protein interactions (PPI), which have garnered significant interest in recent years. Therefore, we developed a method called the quantitative estimate of protein-protein interaction targeting drug-likeness (QEPPI), specifically for early-stage screening of PPI-targeting compounds. QEPPI is an extension of the QED method for PPI-targeting drugs and developed using the QED concept, involving modeling physicochemical properties based on the information available on the drug. QEPPI models the physicochemical properties of compounds that have been reported in the literature to act on PPIs. Compounds in iPPI-DB, which comprises PPI inhibitors and stabilizers, and FDA-approved drugs were evaluated using QEPPI. The results showed that QEPPI is more suitable for the early screening of PPI-targeting compounds than QED. QEPPI was also considered an extended concept of "Rules of Four" (RO4), a PPI inhibitor index proposed by Morelli <i>et al</i>. To compare the discriminatory performance of QEPPI and RO4, we evaluated their discriminatory performance using the datasets of PPI-target compounds and FDA-approved drugs using F-score and other indices. Results of the F-score of RO4 and QEPPI were 0.446 and 0.499, respectively. QEPPI demonstrated better performance and enabled quantification of drug-likeness for early-stage PPI drug discovery. Hence, it could be used as an initial filter for efficient screening of PPI-targeting compounds, which has been difficult in the past.<br>

scholarly journals Modified Peptide Inhibitors of the Keap1–Nrf2 Protein–Protein Interaction Incorporating Unnatural Amino Acids

ChemBioChem ◽  
2018 ◽  
Vol 19 (17) ◽  
pp. 1810-1816 ◽  
Author(s):  
Nikolaos D. Georgakopoulos ◽  
Sandeep K. Talapatra ◽  
Jemma Gatliff ◽  
Frank Kozielski ◽  
Geoff Wells
Keyword(s):  
Amino Acids ◽  
Protein Interaction ◽  
Unnatural Amino Acids ◽  
Peptide Inhibitors ◽  
Protein Protein Interaction ◽  
Nrf2 Protein

scholarly journals Characterization of cytoskeletal protein 4.1R interaction with NHE1 (Na+/H+ exchanger isoform 1)

2012 ◽  
Vol 446 (3) ◽  
pp. 427-435 ◽  
Author(s):  
Wataru Nunomura ◽  
Sheryl P. Denker ◽  
Diane L. Barber ◽  
Yuichi Takakuwa ◽  
Philippe Gascard
Keyword(s):  
Amino Acids ◽  
Protein Interaction ◽  
Cytoskeletal Protein ◽  
Functional Interaction ◽  
Ferm Domain ◽  
Protein Protein Interaction ◽  
Nhe1 Activity ◽  
Acidic Conditions ◽  
Protein 4.1R

NHE1 (Na+/H+ exchanger isoform 1) has been reported to be hyperactive in 4.1R-null erythrocytes [Rivera, De Franceschi, Peters, Gascard, Mohandas and Brugnara (2006) Am. J. Physiol. Cell Physiol. 291, C880–C886], supporting a functional interaction between NHE1 and 4.1R. In the present paper we demonstrate that 4.1R binds directly to the NHE1cd (cytoplasmic domain of NHE1) through the interaction of an EED motif in the 4.1R FERM (4.1/ezrin/radixin/moesin) domain with two clusters of basic amino acids in the NHE1cd, K519R and R556FNKKYVKK, previously shown to mediate PIP2 (phosphatidylinositol 4,5-bisphosphate) binding [Aharonovitz, Zaun, Balla, York, Orlowski and Grinstein (2000) J. Cell. Biol. 150, 213–224]. The affinity of this interaction (Kd=100–200 nM) is reduced in hypertonic and acidic conditions, demonstrating that this interaction is of an electrostatic nature. The binding affinity is also reduced upon binding of Ca2+/CaM (Ca2+-saturated calmodulin) to the 4.1R FERM domain. We propose that 4.1R regulates NHE1 activity through a direct protein–protein interaction that can be modulated by intracellular pH and Na+ and Ca2+ concentrations.

Analysis of physicochemical properties of protein-protein interaction modulators suggests stronger alignment with the “Rule-of-Five”

2021 ◽  
Author(s):  
Jia Truong ◽  
Ashwin George ◽  
Jessica Holien
Keyword(s):  
Physicochemical Properties ◽  
Protein Interaction ◽  
Protein Interactions ◽  
Protein Protein Interactions ◽  
Protein Protein Interaction ◽  
Recent Advances

Despite the important roles played by Protein-Protein Interactions (PPIs) in disease, they have been long considered as ‘undruggable’. However, recent advances have suggested that the PPIs are druggable but may...

scholarly journals Mapping of the Hepatitis B Virus Reverse Transcriptase TP and RT Domains by Transcomplementation for Nucleotide Priming and by Protein-Protein Interaction

1999 ◽  
Vol 73 (3) ◽  
pp. 1885-1893 ◽  
Author(s):  
Robert E. Lanford ◽  
Young-Ho Kim ◽  
Helen Lee ◽  
Lena Notvall ◽  
Burton Beames
Keyword(s):  
Amino Acids ◽  
Reverse Transcriptase ◽  
Protein Interaction ◽  
Protein Interactions ◽  
Rnase H ◽  
Genome Replication ◽  
Protein Protein Interactions ◽  
Stem Loop ◽  
Protein Protein Interaction

ABSTRACT Hepadnavirus polymerases initiate reverse transcription in a protein-primed reaction. We previously described a complementation assay for analysis of the roles of the TP and RT domains of HBV reverse transcriptase (pol) in the priming reaction. Independently expressed TP and RT domains form a complex functional for in vitro priming reactions. To map the minimal functional TP and RT domains, we prepared baculoviruses expressing amino- and carboxyl-terminal deletions of both the TP and RT domains and analyzed the proteins for the ability to participate in transcomplementation for the priming reaction. The minimal TP domain spanned amino acids 20 to 175; however, very little activity was observed without a TP domain spanning amino acids 1 to 199. The minimal RT domain spanned amino acids 300 to 775; however, little activity was observed unless the carboxyl end of the RT domain extended to amino acid 800. Thus, most of the RNase H domain was required. In previous studies, we observed a TP inhibitory domain between amino acids 199 and 344. The current analysis narrowed this domain to residues 300 to 334, which is a portion of the minimal RT domain. In addition, the ability of TP and RT deletion mutants to form stable TP-RT complexes was examined in coimmunoprecipitation assays. The minimal TP and RT domains capable of protein-protein interaction were considerably smaller than the domains required for functional interaction in the transcomplementation assays, and unlike priming activity, TP-RT interaction did not require the epsilon RNA stem-loop. These studies help to further define the complex protein-protein interactions required in HBV genome replication.

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