Identification of protein-protein interfaces by decreased amide proton solvent accessibility

Abstract Background Statistical potentials, also named knowledge-based potentials, are scoring functions derived from empirical data that can be used to evaluate the quality of protein folds and protein–protein interaction (PPI) structures. In previous works we decomposed the statistical potentials in different terms, named Split-Statistical Potentials, accounting for the type of amino acid pairs, their hydrophobicity, solvent accessibility and type of secondary structure. These potentials have been successfully used to identify near-native structures in protein structure prediction, rank protein docking poses, and predict PPI binding affinities. Results Here, we present the SPServer, a web server that applies the Split-Statistical Potentials to analyze protein folds and protein interfaces. SPServer provides global scores as well as residue/residue-pair profiles presented as score plots and maps. This level of detail allows users to: (1) identify potentially problematic regions on protein structures; (2) identify disrupting amino acid pairs in protein interfaces; and (3) compare and analyze the quality of tertiary and quaternary structural models. Conclusions While there are many web servers that provide scoring functions to assess the quality of either protein folds or PPI structures, SPServer integrates both aspects in a unique easy-to-use web server. Moreover, the server permits to locally assess the quality of the structures and interfaces at a residue level and provides tools to compare the local assessment between structures. Server address https://sbi.upf.edu/spserver/.

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Identification of Protein-Protein Interfaces by Amide Proton Exchange Coupled to MALDI-TOF Mass Spectrometry

Mass Spectrometry in Biology & Medicine ◽

10.1007/978-1-59259-719-2_6 ◽

2000 ◽

pp. 91-109

Author(s):

Jeffrey G. Mandell ◽

Arnold M. Falick ◽

Elizabeth A. Komives

Keyword(s):

Mass Spectrometry ◽

Proton Exchange ◽

Amide Proton ◽

Maldi Tof Mass Spectrometry ◽

Maldi Tof ◽

Amide Proton Exchange ◽

Protein Interfaces

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Measurement of Solvent Accessibility at Protein–Protein Interfaces

Protein-Ligand Interactions ◽

10.1385/1-59259-912-5:065 ◽

2005 ◽

pp. 065-080 ◽

Cited By ~ 1

Author(s):

Jeffrey G. Mandell ◽

Abel Baerga-Ortiz ◽

Arnold M. Falick ◽

Elizabeth A. Komives

Keyword(s):

Solvent Accessibility ◽

Protein Interfaces

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Identification of computational hot spots in protein interfaces: combining solvent accessibility and inter-residue potentials improves the accuracy

Bioinformatics ◽

10.1093/bioinformatics/btp240 ◽

2009 ◽

Vol 25 (12) ◽

pp. 1513-1520 ◽

Cited By ~ 179

Author(s):

Nurcan Tuncbag ◽

Attila Gursoy ◽

Ozlem Keskin

Keyword(s):

Hot Spots ◽

Solvent Accessibility ◽

Protein Interfaces

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Aromatic π-networks in Sm/LSm protein interfaces

Facta universitatis - series Physics Chemistry and Technology ◽

10.2298/fupct1401027b ◽

2014 ◽

Vol 12 (1) ◽

pp. 27-39

Author(s):

Luka Breberina ◽

Milan Nikolic ◽

Srdjan Stojanovic

Keyword(s):

Solvent Accessibility ◽

Frequency Of Occurrence ◽

Stabilization Centers ◽

Protein Interfaces ◽

Accessibility Pattern

In this work, we have analyzed the influence of ?-? interactions on stability and properties of Sm/LSm assemblies. Phe residues were found to be involved in ?-? interactions much more frequently than Tyr or His. Similarly, the Phe-Phe ?-? interacting pair had the highest frequency of occurrence. Furthermore, a significant number of ?-networks were observed at the interface of Sm/LSm proteins. Generally speaking, the distance between the interacting pairs was in the range of 5-6 ?. 3? and 7?-networks were found to frequently have plane-plane angles less than 60?. Solvent accessibility pattern of Sm/LSm proteins revealed that all of the interacting residues were from buried areas. Moreover, most of the ?-? interacting residues of Sm/LSm proteins were evolutionary conserved and were in the strand regions. A high percentage of these residues could be considered as stabilization centers that (significantly) contribute to the net stability of Sm/LSm proteins.

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Expression and Characterization of Clustered Charge-to-Alanine Mutants of Low Mr Single-Chain Urokinase-Type Plasminogen Activator

Thrombosis and Haemostasis ◽

10.1055/s-0038-1642397 ◽

1994 ◽

Vol 71 (01) ◽

pp. 134-140 ◽

Cited By ~ 6

Author(s):

S Ueshima ◽

P Holvoet ◽

H R Lijnen ◽

L Nelles ◽

V Seghers ◽

...

Keyword(s):

Plasminogen Activator ◽

Solvent Accessibility ◽

Site Directed Mutagenesis ◽

Clot Lysis ◽

Wild Type ◽

Single Chain ◽

Charged Amino Acids ◽

Type Plasminogen Activator ◽

Urokinase Type Plasminogen Activator ◽

Pharmacokinetic Properties

SummaryIn an effort to modify the fibrinolytic and/or pharmacokinetic properties of recombinant low M r single-chain urokinase-type plasminogen activator (rscu-PA-32k), mutants were prepared by site-directed mutagenesis of clusters of charged amino acids with the highest solvent accessibility. The following mutants of rscu-PA-32k were prepared: LUK-2 (Lys 212, Glu 213 and Asp 214 to Ala), LUK-3 (Lys 243 and Asp 244 to Ala), LUK-4 (Arg 262, Lys 264, Glu 265 and Arg 267 to Ala), LUK-5 (Lys 300, Glu 301 and Asp 305 to Ala) and LUK-6 (Arg 400, Lys 404, Glu 405 and Glu 406 to Ala).The rscu-PA 32k moictic3 were expressed in High Five Ttichoplasiani cells, and purified to humugciicily from the conditioned cell culture medium, with recoveries of 0.8 to 3.7 mg/1. The specific fibrinolytic activities (220,000 to 300,000 IU/mg), the rates of plasminogen activation by the single-chain moieties and the rates of conversion In lwo chain moieties by plasmin were comparable for mutant and wild-type rscu PA 32k moieties, with the exception of LUK-5 which was virtually inactive. Equi-effective lysis (50% in 2 h) of 60 pi 125I-fibrin labeled plasma clots submerged in 0.5 ml normal human plasma was obtained with 0.7 to 0.8 μg/ml of wild-type or mutant rscu-PA-3?.k, except with LUK-5 (no significant lysis with 16 pg/ml). Following bolus injection in hamsters, all rscu-PA-32k moieties had a comparably rapid plasma clearance (1.3 to 2.7 ml/min), as a result of a short initial half-life (1.4 to 2.5 min). In hamsters with pulmonary embolism, continuous intravenous infusion over 60 min at a dose of 1 mg/kg, resulted in 53 to 72% clot lysis with the mutants, but only 23% with LUK-5, as compared to 36% for wild-type rscu-PA-32k.These data indicate that clustered charge-to-alanine mutants of rscu-PA-32k, designed to eliminate charged regions with the highest solvent accessibility, do not have significantly improved functional, fibrinolytic or pharmacokinetic properties.

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