TASK Quarterly   Scientific Bulletin of the Centre of Informatics - Tricity Academic Supercomputer & networK   ISSN 1428-6394

Volume 20, Number 4, 2016



  • Keehyoung Joo, InSuk Joung and Jooyoung Lee An Example of Template Based Protein Structure Modeling by Global Optimization

    CASP (Critical Assessment of protein Structure Prediction) is a community-wide experiment for protein structure prediction taking place every two years since 1994. In CASP11 held in 2014, according to the offiial CASP11 assessment, our method named `nns' was ranked as the second best server method based on models ranked as first out of 81 targets. In `nns', we applied the powerful global optimization method of conformational space annealing to three stages of optimization, including multiple sequence-structure alignment, three-dimensional (3D) chain building, and side-chain remodeling. For the fold recognition, a new alignment method called CRFalign was used. The good performance of the nns server method is attributed to the successful fold recognition carried out by combined methods including CRFalign, and the current modeling formulation incorporating accurate structural aspects collected from multiple templates. In this article, we provide a successful example of `nns' predictions for T0776, for which all details of intermediate modeling data are provided.

  • Martin Zacharias Protein-Protein Docking Refinement Using Restraint Molecular Dynamics Simulations

    A realistic prediction of the structure of protein-protein complexes is of major importance to obtain three-dimensional models for the interaction of proteins to form complexes and assemblies. In addition to the systematic search for putative binding sites on the surface of two binding partners, the second step of a docking effort, the refinement of docked complexes, is a major bottleneck to obtain realistic interaction geometries. Typically, the first initial systematic search employs rigid partner structures or few flexible degrees of freedom, whereas the refinement step involves fully flexible partner structures. The possibility to refine docked complexes using restraint MD simulations combined with an implicit solvent (Generalized Born) model was explored on three example test complexes starting from unbound partner structures. Significant improvement, both in scoring and agreement with the native complex structure after refinement was observed for two test cases. No improvement was found for a test case of a complex with lower binding affinity. The method can be easily applied to any docked protein-protein complex, however, more general applicability requires further improvements in the scoring function.

  • Pawel Dabrowski-Tumanski, Mateusz Sklodowski and Joanna I. Sulkowska Current Approaches to Disentangle the Mystery of Knotted Protein Folding

    The folding of knotted proteins remains a mystery both for theoreticians and experimentalists. Despite the development of new models, the driving force for self-tying remains elusive and the principle of minimal frustration cannot be reproduced in silico. In this paper we review different models used to understand protein self-knotting and suggest, how to improve the structure based model to observe effiient folding. Our preliminary results show, that including information about some amino acids properties, or reducing the set of physical contacts may be beneficial for modeling of the knotted protein folding.

  • Agata P. Perlinska, Joanna M. Macnar and Joanna I. Sulkowska Molecular Dynamics and Structural Comparison Approach to Understanding the Role of Knots in Proteins

    The role of knots in proteins is still unclear. In this short review, we summarize the current knowledge about structural and dynamical differences between knotted and unknotted proteins. We show how the topological difference helps to distinguish the physical properties, characterize the biological activity or identify the biological function of knotted proteins. This knowledge can be used to correctly annotate protein family members and to identify new members.

  • Mateusz Banach, Leszek Konieczny and Irena Roterman Structural Similarity of CheY-like Proteins

    The problem of structural similarity of polypeptide chains of low sequence similarity representing a similar 3D structural form has been the object of analysis of researchers engaged in the protein folding problem. Three homologous proteins of similar biological function with low sequence similarity are the objects of analysis presented in this paper. The structure of a hydrophobic core is used as the criterion for structural similarity assessment of these three proteins. The applied method allows recognition of differentiation in topologically similar structures.

  • Paweł Krupa Treatment of Disulfide Bonds in Coarse-Grained UNRES Force Field

    Disulfide bonds, despite the advances of the computational methods, are underrepresented in theoretical chemistry and the role of disulfide bonds is often diminished in bioinformatical studies. Most of the molecular modeling tools do not allow studying the process of disulfide bond formation and breaking, which is equally important as the sole presence of disulfide bonds in proteins and peptides. The UNRES (UNited RESidue) coarse-grained force field allows treating disulfide bonds in two ways: as static (formed or broken in the simulation) or dynamic (all specified cysteine residues can form and break disulfide bonds during simulation). The comparison between those two approaches of disulfide-bond treatment is presented for protein folding on the example of four small β- and α + β proteins with one, two, three and four disulfide bonds. The results clearly show that proper disulfide bond treatment is important in simulations and significantly enhances the quality of folded structures.

  • Emilia A. Lubecka and Adam Liwo New UNRES Force Field Package with Fortran 90

    UNRES is a coarse-grained model of polypeptide chains. Until now, each version of UNRES (UNRESPACK v. 3.2 and earlier ones) has been written in Fortran 77. Due to the fact that Fortran 77 enables us to use only static arrays, the Fortran 77 version has significant memory problems, and consequently, UNRESPACK has had to be split into many programs. Our recent work was focused on creating a new UNRES package with Fortran 90 (UNRESPACK v. 4.0), based on the previous Fortran 77 versions. Fortran 90 provides dynamic memory allocation, user defined data types, and structuring the code into modules which encompass subroutines, functions, and variables. Moreover, Fortran 90 adds internal functions and subroutines, providing greater flexibility. The whole code of UNRES with Fortran 90 has been restructured, so that it now consists of modules that can be assembled to create the main simulation program and companion programs. This approach enabled us to eliminate the redundancy of the code, while keeping all functions of the package.

  • Joanna Makowska, Wioletta Żmudzińska, Dariusz Wyrzykowski, Krzysztof Brzozowski, Honorata Zblewska and Lech Chmurzyński Probing of Cu2+ Ions Binding to Aβ(5-16) Peptide Using ITC Measurements and MD Simulations

    It is shown that probably three residues: His6, His14 and His16 in the original sequence Aβ(1−42) serve as metal-binding sites for Cu2+ ions. On the other hand, there is a possibility that only one of them plays a crucial role in the formation of the {Aβ(1−42) –Cu2+ } complex. The isothermal titration calorimetry (ITC) measurements supported by molecular dynamic simulation (MD) with the NMR-derived restrains were used to investigate the interactions of Cu2+ with Aβ(5−16) , a fragment of the Aβ(1−42) protein, with the following sequence: Ac –Arg –His –Asp –Ser –Gly –Tyr –Glu –Val –His –His –Gln –Lys –NH2 , termed HZ1. The conditional thermodynamic parameters suggest that the formation of the Cu2+ –HZ1 complex is both an enthalpy and entropy driven process under the experimental conditions. The studies presented here (after comparison with our previous results) show that the affinity of peptides to copper metal ions depends on two factors: the primary structure (amino acid composition) and the shape of the peptide conformation adopted.

  • Magdalena A. Mozolewska Influence of Substitutions of Isu1 Residues on Binding to Jac1 protein

    The iron-sulfur (Fe/S) clusters are the most ancient co-factors of proteins involved in the most essential processes in bacterial systems and yeast, such as Saccharomyces cerevisiae. The main protein involved in the Fe/S cluster transfer is the Iron sulfur cluster assembly protein 1 (Isu1), which interacts with Jac1 during one of the stages of the Fe/S cluster biogenesis cycle forming a binary complex. In this work, the interaction interface of Isu1 was investigated by selective substitutions of amino-acid residues to understand their role in binding to the Jac1 protein. An initial alanine scan was done to limit the number of possible residues subjected to the replacement and to confirm the previously obtained results. Then, MD simulations using the coarse-grained UNRES force field were run for two selected mutants: L63 V72 F94 and L63 V64 G65 D71 . The analysis of the dynamics and interaction patterns of the Isu1-Jac1 complexes confirmed that the investigated residues played an important role in their binding.