Ihsan A Shehadi

Publications (5)2.93 Total impact

• Article: Active site prediction for comparative model structures with thematics.

  Ihsan A Shehadi, Alexej Abyzov, Alper Uzun, Ying Wei, Leonel F Murga, Valentin Ilyin, Mary Jo Ondrechen
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  ABSTRACT: THEMATICS (Theoretical Microscopic Titration Curves) is a simple, reliable computational predictor of the active sites of enzymes from structure. Our method, based on well-established Finite Difference Poisson-Boltzmann techniques, identifies the ionisable residues with anomalous predicted titration behavior. A cluster of two or more such perturbed residues is a very reliable predictor of the active site. The protein does not have to bear any resemblance in sequence or structure to any previously characterized protein, but the method does require the three-dimensional structure. We now present evidence that THEMATICS can also locate the active site in structures built by comparative modeling from similar structures. Results are given for a total of 21 sets of proteins, including 21 templates and 83 comparative model structures. Detailed results are presented for three sets of orthologous proteins (Triosephosphate isomerase, 6-Hydroxymethyl-7,8-dihydropterin pyrophosphokinase, and Aspartate aminotransferase) and for one set of human homologues of Aldose reductase with different functions. THEMATICS correctly locates the active site in the model structures. This suggests that the method can be applicable to a much larger set of proteins for which an experimentally determined structure is unavailable. With a few exceptions, the predicted active sites in the comparative model structures are similar to that of the corresponding template structure.
  Journal of Bioinformatics and Computational Biology 03/2005; 3(1):127-43.
• Article: THEMATICS is Effective for Active Site Prediction in Comparative

  Ihsan A Shehadi, Alper Uzun, Leonel F Murga, Valentin Ilyin, Mary Jo Ondrechen
  [show abstract] [hide abstract]
  ABSTRACT: THEMATICS (Theoretical Microscopic Titration Curves) is a simple, reliable computational predictor of the active sites of enzymes from structure. Our method, based on well-established Finite Difference Poisson-Boltzmann techniques, identifies the ionisable residues with anomalous predicted titration behaviour. A cluster of two or more such perturbed residues is a very reliable predictor of the active site. The power of the method is that it only requires the three-dimensional structure as input. The protein does not have to bear any resemblance in sequence or structure to any previously characterized protein. The disadvantage of the method is that it does require the structure. We now present evidence that THEMATICS can also locate the active site in structures built by comparative modelling from similar structures. Results are given for three sets of orthologous proteins (Triosephosphate isomerase, 6-Hydroxymethyl-7,8dihydropterin pyrophosphokinase, and Aspartate aminotransferase) and for one set of human homologues of Aldose reductase with different functions. In all of the cases studied, THEMATICS correctly locates the active site in the model structures. This suggests that the method can be applicable to proteins for which an experimentally determined structure is unavailable.
  02/2004;
• Source

  Available from: Mary Jo Ondrechen

  Conference Proceeding: THEMATICS is Effective for Active Site Prediction in Comparative Model Structures.

  Ihsan A. Shehadi, Alper Uzun, Leonel F. Murga, Valentin A. Ilyin, Mary Jo Ondrechen
  Second Asia-Pacific Bioinformatics Conference (APBC 2004), January 18-22, 2004, Dunedin, New Zealand; 01/2004
• Article: Future directions in protein function prediction.

  Ihsan A Shehadi, Huyuan Yang, Mary Jo Ondrechen
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  ABSTRACT: New directions in computational methods for the prediction of protein function are discussed. THEMATICS, a method for the location and characterization of the active sites of enzymes, is featured. THEMATICS, for Theoretical Microscopic Titration Curves, is based on well-established finite-difference Poisson-Boltzmann methods for computing the electric field function of a protein. THEMATICS requires only the structure of the subject protein and thus may be applied to proteins that bear no similarity in structure or sequence to any previously characterized protein. The unique features of catalytic sites in proteins are discussed. Discussion of the chemical basis for the predictive powers of THEMATICS is featured in this paper. Some results are given for three illustrative examples: HIV-1 protease, human apurinic/apyrimidinic endonuclease, and human adenosine kinase.
  Molecular Biology Reports 01/2003; 29(4):329-35. · 2.93 Impact Factor
• Source

  Available from: Giovanni Villani

  Article: Theory of Electroabsorption Spectroscopy in Pyrazine-Bridged Ru Dimers

  Alessandro Ferretti, Alessandro Lami, Leonel F. Murga, Ihsan A. Shehadi, Mary Jo Ondrechen, Giovanni Villani
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  ABSTRACT: A theoretical study of near-IR−vis electroabsorption spectroscopy (Stark effect) for the Creutz−Taube ion, a pyrazine-bridged mixed-valence Ru dimer, and for its homovalent +4 analogue is presented. A vibronic model that takes into account correlation effects is considered for the calculation of absorption line shape profiles, also in the presence of an external static electric field. The model also incorporates the orientation of molecules with respect to the applied field and the polarization of the incident light and accounts for the essential features of the difference spectra that have been observed experimentally.
  03/1999;