Researcher:
Gür, Mert

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PhD Student

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Mert

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Gür

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Gür, Mert

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2009 - 200912010 - 20137

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Now showing 1 - 8 of 8
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    Quasi-harmonic fluctuations of two bound peptides
    (Wiley-Blackwell, 2012) N/A; Department of Chemical and Biological Engineering; Gür, Mert; Erman, Burak; PhD Student; Faculty Member; Department of Chemical and Biological Engineering; Graduate School of Sciences and Engineering; College of Engineering; 216930; 179997
    Binding of two short peptides of sequences ASN-ASP-MET-PHE-ARG-LEU and LEU-LEU-PHE-MET-GLN-HIS and their bound complex structures is studied. Molecular dynamic simulations of the three structures around their respective minimum energy conformations are performed and a quasi-harmonic analysis is performed over the trajectories generated. The fluctuation correlation matrix is constructed for all C-alpha-atoms of the peptides for the full trajectory. The spring constant matrix between peptide C-alpha-atoms is obtained from the correlation matrix. Statistical thermodynamics of fluctuations, the energies, entropies, and the free energies of binding are discussed in terms of the quasi-harmonic model. Sites contributing to the stability of the system and presenting high affinity for binding are determined. Contribution of hydrophobic forces to binding is discussed. Quasi-harmonic approximation identifies the essential subspace of motions, the important interactions, and binding sites, gives the energetic contribution of each individual interaction, and filters out noise observed in molecular dynamics owing to uncorrelated motions. Comparison of the molecular dynamics results with those of the quasi-harmonic model shows the importance of entropy change, resulting from water molecules being liberated from the surfaces of the two peptides upon binding.
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    Quasi-harmonic analysis of mode coupling in fluctuating native proteins
    (Iop Publishing Ltd, 2010) N/A; Department of Chemical and Biological Engineering; Gür, Mert; Erman, Burak; PhD Student; Faculty Member; Department of Chemical and Biological Engineering; Graduate School of Sciences and Engineering; College of Engineering; 216930; 179997
    Mode coupling and anharmonicity in a native fluctuating protein are investigated in modal space by projecting the motion along the eigenvectors of the fluctuation correlation matrix. The probability distribution of mode fluctuations is expressed in terms of tensorial Hermite polynomials. Molecular dynamics trajectories of Crambin are generated and used to evaluate the terms of the polynomials and to obtain the modal energies. The energies of a few modes exhibit large deviations from the harmonic energy of kT/2 per mode, resulting from coupling to the surroundings, or to another specific mode or to several other modes. Slowest modes have energies that are below that of the harmonic, and a few fast modes have energies significantly larger than the harmonic. Detailed analysis of the coupling of these modes to others is presented in terms of the lowest order two-mode coupling terms. Finally, the effects of mode coupling on conformational properties of the protein are investigated.
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    Coupling between energy and residue position fluctuations in native proteins
    (IEEE, 2010) Department of Chemical and Biological Engineering; N/A; Erman, Burak; Gür, Mert; Faculty Member; PhD Student; Department of Chemical and Biological Engineering; College of Engineering; Graduate School of Sciences and Engineering; 179997; 216930
    The coupling between energy fluctuations and positional fluctuations in molecular dynamics trajectories of Crambin at 310 K is studied. Coupling with energy fluctuation is evaluated for both atomic positions and residue positions. Couplings show values which fluctuate around the previously proposed theoretical value under harmonic approximation. The magnitude of these correlations is in agreement, on the average, with the harmonic approximation. Additionally coupling between energy fluctuations and atom-atom distance fluctuations are evaluated. This coupling indicates how much each interaction among different atoms/residues is correlated with the protein's total energy fluctuations. Some atom's/residue's interactions have shown outstanding correlation. Moreover coupling of residue fluctuations between different modes is studied. © 2009 IEEE.
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    Anharmonicity, mode-coupling and entropy in a fluctuating native protein
    (Iop Publishing Ltd, 2010) N/A; Department of Physics; Department of Computer Engineering; N/A; Department of Chemical and Biological Engineering; Kabakçıoğlu, Alkan; Yüret, Deniz; Gür, Mert; Erman, Burak; Faculty Member; Faculty Member; PhD Student; Faculty Member; Department of Physics; Department of Computer Engineering; Department of Chemical and Biological Engineering; College of Sciences; College of Engineering; Graduate School of Sciences and Engineering; College of Engineering; 49854; 179996; 216930; 179997
    We develop a general framework for the analysis of residue fluctuations that simultaneously incorporates anharmonicity and mode-coupling in a unified formalism. We show that both deviations from the Gaussian model are important for modeling the multidimensional energy landscape of the protein Crambin (1EJG) in the vicinity of its native state. the effect of anharmonicity and mode-coupling on the fluctuational entropy is in the order of a few percent.
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    Protein folding using coarse-grained optimal control and molecular dynamics
    (IFAC, 2011) Department of Chemical and Biological Engineering; N/A; Arkun, Yaman; Gür, Mert; Faculty Member; PhD Student; Department of Chemical and Biological Engineering; The Center for Computational Biology and Bioinformatics (CCBB); College of Engineering; Graduate School of Sciences and Engineering; 108526; 216930
    Protein folding is formulated as a moving horizon optimal control problem. We present a novel method that combines coarse-grained optimal control and molecular dynamics to generate dynamical folding trajectories with full atomic details. The method is applied to a benchmark protein, Villin headpiece.
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    PublicationOpen Access
    Computational design of new peptide inhibitors for amyloid beta (A beta) aggregation in Alzheimer's disease: application of a novel methodology
    (Public Library of Science, 2013) Eskici, Gözde; Gür, Mert; PhD Student; The Center for Computational Biology and Bioinformatics (CCBB); College of Engineering
    Alzheimer's disease is the most common form of dementia. It is a neurodegenerative and incurable disease that is associated with the tight packing of amyloid fibrils. This packing is facilitated by the compatibility of the ridges and grooves on the amyloid surface. The GxMxG motif is the major factor creating the compatibility between two amyloid surfaces, making it an important target for the design of amyloid aggregation inhibitors. In this study, a peptide, experimentally proven to bind A beta 40 fibrils at the GxMxG motif, was mutated by a novel methodology that systematically replaces amino acids with residues that share similar chemical characteristics and subsequently assesses the energetic favorability of these mutations by docking. Successive mutations are combined and reassessed via docking to a desired level of refinement. This methodology is both fast and efficient in providing potential inhibitors. Its efficiency lies in the fact that it does not perform all possible combinations of mutations, therefore decreasing the computational time drastically. The binding free energies of the experimentally studied reference peptide and its three top scoring derivatives were evaluated as a final assessment/valuation. The potential of mean forces (PMFs) were calculated by applying the Jarzynski's equality to results of steered molecular dynamics simulations. For all of the top scoring derivatives, the PMFs showed higher binding free energies than the reference peptide substantiating the usage of the introduced methodology to drug design.
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    PublicationOpen Access
    Combining optimal control theory and molecular dynamics for protein folding
    (Public Library of Science, 2012) Department of Chemical and Biological Engineering; Arkun, Yaman; Gür, Mert; Faculty Member; PhD Student; Department of Chemical and Biological Engineering; College of Engineering; 108526; N/A
    A new method to develop low-energy folding routes for proteins is presented. The novel aspect of the proposed approach is the synergistic use of optimal control theory with Molecular Dynamics (MD). In the first step of the method, optimal control theory is employed to compute the force field and the optimal folding trajectory for the C-alpha atoms of a Coarse-Grained (CG) protein model. The solution of this CG optimization provides an harmonic approximation of the true potential energy surface around the native state. In the next step CG optimization guides the MD simulation by specifying the optimal target positions for the C-alpha atoms. In turn, MD simulation provides an all-atom conformation whose C-alpha positions match closely the reference target positions determined by CG optimization. This is accomplished by Targeted Molecular Dynamics (TMD) which uses a bias potential or harmonic restraint in addition to the usual MD potential. Folding is a dynamical process and as such residues make different contacts during the course of folding. Therefore CG optimization has to be reinitialized and repeated over time to accomodate these important changes. At each sampled folding time, the active contacts among the residues are recalculated based on the all-atom conformation obtained from MD. Using the new set of contacts, the CG potential is updated and the CG optimal trajectory for the C-alpha atoms is recomputed. This is followed by MD. Implementation of this repetitive CG optimization - MD simulation cycle generates the folding trajectory. Simulations on a model protein Villin demonstrate the utility of the method. Since the method is founded on the general tools of optimal control theory and MD without any restrictions, it is widely applicable to other systems. It can be easily implemented with available MD software packages.
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    PublicationOpen Access
    Statistical thermodynamics of residue fluctuations in native proteins
    (American Institute of Physics (AIP) Publishing, 2009) Department of Electrical and Electronics Engineering; Department of Chemical and Biological Engineering; Yoğurtçu, Osman Nuri; Gür, Mert; Erman, Burak; PhD Student; Faculty Member; Department of Electrical and Electronics Engineering; Department of Chemical and Biological Engineering; College of Engineering; N/A; N/A; 179997
    Statistical thermodynamics of residue fluctuations of native proteins in a temperature, pressure, and force reservoir is formulated. The general theory is discussed in terms of harmonic and anharmonic fluctuations of residues. The two elastic network models based on the harmonic approximation, the anisotropic network and the Gaussian network models are discussed as the limiting cases of the general theory. The heat capacity and the correlations between the energy fluctuations and residue fluctuations are obtained for the harmonic approximation. The formulation is extended to large fluctuations of residues in order to account for effects of anharmonicity. The fluctuation probability function is constructed for this purpose as a tensorial Hermite series expansion with higher order moments of fluctuations as coefficients. Evaluation of the higher order moments using the proposed statistical thermodynamics model is explained. The formulation is applied to a hexapeptide and the fluctuations of residues obtained by molecular dynamics simulations are characterized in the framework of the model developed. In particular, coupling of two different modes in the nonlinear model is discussed in detail.