Predrag Kukić

Publications (2)5.91 Total impact

• Source

  Available from: Jens Erik Nielsen

  Article: Electrostatics in proteins and protein-ligand complexes.

  Predrag Kukić, Jens Erik Nielsen
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  ABSTRACT: Accurate computational methods for predicting electrostatic energies are of major importance for our understanding of protein energetics in general for computer-aided drug design as well as for the design of novel biocatalysts and protein therapeutics. Electrostatic energies are of particular importance in such applications as virtual screening, drug design and protein-protein docking due to the high charge density of protein ligands and small-molecule drugs, and the frequent protonation state changes observed when drugs bind to their protein targets. Therefore, the development of a reliable and fast algorithm for the evaluation of electrostatic free energies, as an important contributor to the overall protein energy function, has been the focus for many scientists over the past three decades. In this review we describe the current state-of-the-art in modeling electrostatic effects in proteins and protein-ligand complexes. We focus mainly on the merits and drawbacks of the continuum methodology, and speculate on future directions in refining algorithms for calculating electrostatic energies in proteins using experimental data.
  Future medicinal chemistry 04/2010; 2(4):647-66. · 2.52 Impact Factor
• Source

  Available from: Jens Erik Nielsen

  Article: Improving the analysis of NMR spectra tracking pH-induced conformational changes: removing artefacts of the electric field on the NMR chemical shift.

  Predrag Kukić, Damien Farrell, Chresten R Søndergaard, Una Bjarnadottir, John Bradley, Gianluca Pollastri, Jens Erik Nielsen
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  ABSTRACT: pH-induced chemical shift perturbations (CSPs) can be used to study pH-dependent conformational transitions in proteins. Recently, an elegant principal component analysis (PCA) algorithm was developed and used to study the pH-dependent structural transitions in bovine beta-lactoglobulin (betaLG) by analyzing its NMR pH-titration spectra. Here, we augment this analysis method by filtering out changes in the NMR chemical shift that stem from effects that are electrostatic in nature. Specifically, we examine how many CSPs can be explained by purely electrostatic effects arising from titrational events in betaLG. The results show that around 20% of the amide nuclei CSPs in betaLG originate exclusively from "through-space" electric field effects. A PCA of NMR data where electric field artefacts have been removed gives a different picture of the pH-dependent structural transitions in betaLG. The method implemented here is well suited to be applied on a whole range of proteins, which experience at least one pH-dependent conformational change. Proteins 2010. (c) 2009 Wiley-Liss, Inc.
  Proteins Structure Function and Bioinformatics 09/2009; 78(4):971-84. · 3.39 Impact Factor