Analysis of accessible surface of residues in proteins.
ABSTRACT: We analyzed the total, hydrophobic, and hydrophilic accessible surfaces (ASAs) of residues from a nonredundant bank of 587 3D structure proteins. In an extended fold, residues are classified into three families with respect to their hydrophobicity balance. As expected, residues lose part of their solvent-accessible surface with folding but the three groups remain. The decrease of accessibility is more pronounced for hydrophobic than hydrophilic residues. Amazingly, Lysine is the residue with the largest hydrophobic accessible surface in folded structures. Our analysis points out a clear difference between the mean (other studies) and median (this study) ASA values of hydrophobic residues, which should be taken into consideration for future investigations on a protein-accessible surface, in order to improve predictions requiring ASA values. The different secondary structures correspond to different accessibility of residues. Random coils, turns, and beta-structures (outside beta-sheets) are the most accessible folds, with an average of 30% accessibility. The helical residues are about 20% accessible, and the difference between the hydrophobic and the hydrophilic residues illustrates the amphipathy of many helices. Residues from beta-sheets are the most inaccessible to solvent (10% accessible). Hence, beta-sheets are the most appropriate structures to shield the hydrophobic parts of residues from water. We also show that there is an equal balance between the hydrophobic and the hydrophilic accessible surfaces of the 3D protein surfaces irrespective of the protein size. This results in a patchwork surface of hydrophobic and hydrophilic areas, which could be important for protein interactions and/or activity.
Project description:BACKGROUND: Depending on chemical features residues have preferred locations -- interior or exterior -- in protein structures, which also determine how many other residues are found around them. The close packing of residues is the hallmark of protein interior and protein-protein interaction sites. RESULTS: The average values of accessible surface area (ASA) and partner number (PN, the number of other residues within a distance of 4.5 A from any atom of a given residue) of different residues have been determined and a webserver, ContPlot has been designed to display these values (relative to the average values) along the protein sequence. This would be useful to visually identify residues that are densely packed, or those involved in protein-protein interactions. The skewness observed in the distribution of PNs is indicative of the hydrophobic or hydrophilic nature of the residue. The variation of ASA with PN can be analytically expressed in terms of a cubic equation. These equations (one for each residue) can be used to estimate the ASA of a polypeptide chain using the PNs of the individual residues in the structure. CONCLUSION: The atom-based PNs (obtained by counting surrounding atoms) are highly correlated to the residue-based PN, indicating that the latter can adequately capture the atomic details of packing. The average values of ASA and PN associated with each residue should be useful in protein structure prediction or fold-recognition algorithm. ContPlot would provide a handy tool to assess the importance of a residue in the protein structure or interaction site.
Project description:Methods of structural and statistical analysis of the relation between the sequence and secondary and three-dimensional structures are developed. About 5000 secondary structures of immunoglobulin molecules from the Kabat data base were predicted. Two statistical analyses of amino acids reveal 47 universal positions in strands and loops. Eight universally conservative positions out of the 47 are singled out because they contain the same amino acid in > 90% of all chains. The remaining 39 positions, which we term universally alternative positions, were divided into five groups: hydrophobic, charged and polar, aromatic, hydrophilic, and Gly-Ala, corresponding to the residues that occupied them in almost all chains. The analysis of residue-residue contacts shows that the 47 universal positions can be distinguished by the number and types of contacts. The calculations of contact maps in the 29 antibody structures revealed that residues in 24 of these 47 positions have contacts only with residues of antiparallel beta-strands in the same beta-sheet and residues in the remaining 23 positions always have far-away contacts with residues from other beta-sheets as well. In addition, residues in 6 of the 47 universal positions are also involved in interactions with residues of the other variable or constant domains.
Project description:Glycosyl hydrolases hydrolyze the glycosidic bond either in carbohydrates or between carbohydrate and non-carbohydrate moiety. The beta-glucuronidase (beta D-glucuronoside glucuronosohydrolase; EC 188.8.131.52) enzyme belongs to the family-2 glycosyl hydrolase. The E. coli borne beta-glucuronidase gene (uidA) was devised as a gene fusion marker in plant genetic transformation experiments. Recent plant transformation vectors contain a novel beta-glucuronidase (gusA) derived from Staphylococcus sp. RLH1 for E. coli uidA. It is known to have a ten fold higher sensitivity compared to E. coli beta-glucuronidase. The functional superiority of Staphylococcus (gusA) over E. coli (uidA) activity is not fully known. The comparison of secondary structural elements among them revealed an increased percentage of random coils in Staphylococcus beta-glucuronidase. The 3D model of gusA shows catalytic site residues 396Glu, 508Glu and 471Tyr of gusA in loop regions. Accessible surface area (ASA) calculations on the 3D model showed increased ASA for active site residues in Staphylococcus beta-glucuronidase. Increased random coil, the presence of catalytic residues in loops, greater solvent accessibility of active residues and increased charged residues in gusA of Staphylococcus might facilitate interaction with the solvent. This hypothesizes the enhanced catalytic activity of beta-glucuronidase in Staphylococcus sp. RLH1 compared to that in E. coli.
Project description:A high-resolution solution structure of bucandin, a neurotoxin from Malayan krait (Bungarus candidus), was determined by (1)H-NMR spectroscopy and molecular dynamics. The average backbone root-mean-square deviation for the 20 calculated structures and the mean structure is 0.47 A (1 A=0.1 nm) for all residues and 0.24 A for the well-defined region that spans residues 23-58. Secondary-structural elements include two antiparallel beta-sheets characterized by two and four strands. According to recent X-ray analysis, bucandin adopts a typical three-finger loop motif and yet it has some peculiar characteristics that set it apart from other common alpha-neurotoxins. The presence of a fourth strand in the second antiparallel beta-sheet had not been observed before in three-finger toxins, and this feature was well represented in the NMR structure. Although the overall fold of the NMR structure is similar to that of the X-ray crystal structure, there are significant differences between the two structures that have implications for the pharmacological action of the toxin. These include the extent of the beta-sheets, the conformation of the region spanning residues 42-49 and the orientation of some side chains. In comparison with the X-ray structure, the NMR structure shows that the hydrophobic side chains of Trp(27) and Trp(36) are stacked together and are orientated towards the tip of the middle loop. The NMR study also showed that the two-stranded beta-sheet incorporated in the first loop, as defined by residues 1-22, and the C-terminus from Asn(59), is probably flexible relative to the rest of the molecule. On the basis of the dispositions of the hydrophobic and hydrophilic side chains, the structure of bucandin is clearly different from those of cytotoxins.
Project description:In 1953, Pauling and Corey predicted that enantiomeric ?-sheet peptides would coassemble into so-called "rippled" ?-sheets, in which the ?-sheets would consist of alternating l- and d-peptides. To date, this phenomenon has been investigated primarily with amphipathic peptide sequences composed of alternating hydrophilic and hydrophobic amino acid residues. Here, we show that enantiomers of a fragment of the amyloid-? (A?) peptide that does not follow this sequence pattern, amyloid-? (16-22), readily coassembles into rippled ?-sheets. Equimolar mixtures of enantiomeric amyloid-? (16-22) peptides assemble into supramolecular structures that exhibit distinct morphologies from those observed by self-assembly of the single enantiomer pleated ?-sheet fibrils. Formation of rippled ?-sheets composed of alternating l- and d-amyloid-? (16-22) is confirmed by isotope-edited infrared spectroscopy and solid-state NMR spectroscopy. Sedimentation analysis reveals that rippled ?-sheet formation by l- and d-amyloid-? (16-22) is energetically favorable relative to self-assembly into corresponding pleated ?-sheets. This work illustrates that coassembly of enantiomeric ?-sheet peptides into rippled ?-sheets is not limited to peptides with alternating hydrophobic/hydrophilic sequence patterns, but that a broader range of sequence space is available for the design and preparation of rippled ?-sheet materials.
Project description:Mitigation of environmental dust from surfaces becomes one of the challenges for maintaining the optical characteristics of surfaces. Dust repelling from hydrophobic and hydrophilic surfaces under vibrational excitation is investigated and the percentage of dust repelled from surfaces is evaluated. The characteristics of the dust particles are examined and dust adhesion on surfaces under molecular forces (van der Walls) is explored. High speed recording system is utilized to monitor dust repelling from the surfaces. The dust residues, which are not repelled from the sample surfaces, are analyzed and the percentage of area coverage of the dust repelled from the surfaces is assessed. The repelling height of the dust is predicted analytically, and the findings are compared with the experimental data. Findings revealed that the analytical predictions of dust repelling height are in good agreement with the experimental data. Due to none-stoichiometric elemental compositions in the dust compounds, ionic forces are created while forming the cluster-like structures because of particle adhesion. The vibrational excitation repels dust from sample surfaces in the form of cluster-like structures. Dust repelled from hydrophobic surface results in a larger clean area on the hydrophobic surface (80% of total surface area) than that of the hydrophilic surface (20% of total surface area).
Project description:The nipple array is a submicrometre-scale structure found on the cuticle surfaces of various invertebrate taxa. Corneal nipples are an antiglare surface in nocturnal insects, but the functional significance of the nipple array has not been experimentally investigated for aquatic organisms. Using nanopillar sheets as a mimetic model of the nipple array, we demonstrated that significantly fewer bubbles adhered to the nanopillar surface versus a flat surface when the sheets were hydrophilic. Many more bubbles adhered to the hydrophobic surface than the hydrophilic surfaces. Bubbles on the body surface may cause buoyancy problems, movement interference and water flow occlusion. Here, bubble repellence is proposed as a function of the hydrophilic nipple array in aquatic invertebrates and its properties are considered based on bubble adhesion energy.
Project description:Most of hydrophilic and hydrophobic residues are thought to be exposed and buried in proteins, respectively. In contrast to the majority of the existing studies on protein folding characteristics using protein structures, in this study, our aim was to design predictors for estimating relative solvent accessibility (RSA) of amino acid residues to discover protein folding characteristics from sequences.The proposed 20 real-value RSA predictors were designed on the basis of the support vector regression method with a set of informative physicochemical properties (PCPs) obtained by means of an optimal feature selection algorithm. Then, molecular dynamics simulations were performed for validating the knowledge discovered by analysis of the selected PCPs.The RSA predictors had the mean absolute error of 14.11% and a correlation coefficient of 0.69, better than the existing predictors. The hydrophilic-residue predictors preferred PCPs of buried amino acid residues to PCPs of exposed ones as prediction features. A hydrophobic spine composed of exposed hydrophobic residues of an ?-helix was discovered by analyzing the PCPs of RSA predictors corresponding to hydrophobic residues. For example, the results of a molecular dynamics simulation of wild-type sequences and their mutants showed that proteins 1MOF and 2WRP_H16I (Protein Data Bank IDs), which have a perfectly hydrophobic spine, have more stable structures than 1MOF_I54D and 2WRP do (which do not have a perfectly hydrophobic spine).We identified informative PCPs to design high-performance RSA predictors and to analyze these PCPs for identification of novel protein folding characteristics. A hydrophobic spine in a protein can help to stabilize exposed ?-helices.
Project description:We present a new database of computational hot spots in protein interfaces: HotSprint. Hot spots are residues comprising only a small fraction of interfaces yet accounting for the majority of the binding energy. HotSprint contains data for 35 776 protein interfaces among 49 512 protein interfaces extracted from the multi-chain structures in Protein Data Bank (PDB) as of February 2006. The conserved residues in interfaces with certain buried accessible solvent area (ASA) and complex ASA thresholds are flagged as computational hot spots. The predicted hot spots are observed to correlate with the experimental hot spots with an accuracy of 76%. Several machine-learning methods (SVM, Decision Trees and Decision Lists) are also applied to predict hot spots, results reveal that our empirical approach performs better than the others. A web interface for the HotSprint database allows users to browse and query the hot spots in protein interfaces. HotSprint is available at http://prism.ccbb.ku.edu.tr/hotsprint; and it provides information for interface residues that are functionally and structurally important as well as the evolutionary history and solvent accessibility of residues in interfaces.
Project description:Hydrophobins are small (ca. 100 amino acids) secreted fungal proteins that are characterized by the presence of eight conserved cysteine residues and by a typical hydropathy pattern. Class I hydrophobins self-assemble at hydrophilic-hydrophobic interfaces into highly insoluble amphipathic membranes, thereby changing the nature of surfaces. Hydrophobic surfaces become hydrophilic, while hydrophilic surfaces become hydrophobic. To see whether surface properties of assembled hydrophobins can be changed, 25 N-terminal residues of the mature SC3 hydrophobin were deleted (TrSC3). In addition, the cell-binding domain of fibronectin (RGD) was fused to the N terminus of mature SC3 (RGD-SC3) and TrSC3 (RGD-TrSC3). Self-assembly and surface activity were not affected by these modifications. However, physiochemical properties at the hydrophilic side of the assembled hydrophobin did change. This was demonstrated by a change in wettability and by enhanced growth of fibroblasts on Teflon-coated with RGD-SC3, TrSC3, or RGD-TrSC3 compared to bare Teflon or Teflon coated with SC3. Thus, engineered hydrophobins can be used to functionalize surfaces.