Researcher:
Reşat, Haluk

Profile Picture
ORCID

Job Title

Faculty Member

First Name

Haluk

Last Name

Reşat

Name

Name Variants

Reşat, Haluk

Email Address

Birth Date

Filters

1996 - 1999112000 - 20025

Advanced Search

Filter by

Settings

Researcher Of Publications: search.filters.isAuthorOfPublication.ed4e9036-b880-4465-a9fb-0065979ae215

Search Results

Now showing 1 - 10 of 16
  • Placeholder
    PublicationMetadata only
    Conformational properties of amphotericin B amide derivatives - impact on selective toxicity
    (Springer, 2000) Sungur, Fethiye Aylin; Beginski, Maciej; Borowski, Edward; Aviyente, Viktorya; Department of Physics; Reşat, Haluk; Faculty Member; Department of Physics; College of Sciences; N/A
    Even though it is highly toxic, Amphotericin B (AmB), an amphipathic polyene macrolide antibiotic, is used in the treatment of severe systemic fungal infections as a life-saving drug. To examine the influence of conformational factors on selective toxicity of these compounds, we have investigated the conformational properties of five AmB amide derivatives. It was found that the extended conformation with torsional angles (ΦΨ)=(290°, 180°) is a common minimum of the potential energy surfaces (PES) of unsubstituted AmB and its amide derivatives. The extended conformation of the studied compounds allows for the formation of an intermolecular hydrogen bond network between adjacent antibiotic molecules in the open channel configuration. Therefore, the extended conformation is expected to be the dominant conformer in an open AmB (or its amide derivatives) membrane channel. The derivative compounds for calculations were chosen according to their selective toxicity compared to AmB and they had a wide range of selective toxicity. Except for two AmB derivatives, the PES maps of the derivatives reveal that the molecules can coexist in more than one conformer. Taking into account the cumulative conclusions drawn from the earlier MD simulation studies of AmB membrane channel, the results of the potential energy surface maps, and the physical considerations of the molecular structures, we hypothesize a new model of structure-selective toxicity of AmB derivatives. In this proposed model the presence of the extended conformation as the only well defined global conformer for AmB derivatives is taken as the indicator of their higher selective toxicity. This model successfully explains our results. To further test our model, we also investigated an AmB derivative whose selective toxicity has not been experimentally measured before. Our prediction for the selective toxicity of this compound can be tested in experiments to validate or invalidate the proposed model.
  • Placeholder
    PublicationMetadata only
    The sensitivity of conformational free energies of the alanine dipeptide to atomic site charges
    (Wiley, 1997) Maye, Peter V.; Mezei, Mihaly; Department of Physics; Reşat, Haluk; Faculty Member; Department of Physics; College of Sciences; N/A
    Different atomic point charge sets are obtained for the are and C7,eq conformations of the alanine dipeptide by fitting the charges of each conformation to the respective ab initio electrostatic potential surfaces both individually and simultaneously, in both the united atom and the all-atom representations. Using these charge sets, the sensitivity of the relative conformational aqueous free energies to the atomic site charges is investigated. For this particular system, we find that the solute-water contributions to the conformational free energy differences have a rather weak dependence on site charges; the calculated intramolecular contributions, however, show a rather strong dependence on the atomic site charges. It is suggested that the calculated results for the alanine dipeptide using a single, simultaneously fit set of charges for both conformations are in better agreement with experiments than the calculations carried out with charges determined individually for each conformation. © 1997 John Wiley & Sons, Inc.
  • Placeholder
    PublicationMetadata only
    Conformational properties of amphotericin b amide derivatives - impact on selective toxicity
    (Springer, 2000) Sungur, F. Aylin; Baginski, Maciej; Borowski, Edward; Aviyente, Viktorya; Department of Physics; Reşat, Haluk; Faculty Member; Department of Physics; College of Sciences; N/A
    Even though it is highly toxic, Amphotericin B (AmB), an amphipathic polyene macrolide antibiotic, is used in the treatment of severe systemic fungal infections as a life-saving drug. To examine the influence of conformational factors on selective toxicity of these compounds, we have investigated the conformational properties of five AmB amide derivatives. It was found that the extended conformation with torsional angles (phi,psi)=(290 degrees,180 degrees ) is a common minimum of the potential energy surfaces (PES) of unsubstituted AmB and its amide derivatives. The extended conformation of the studied compounds allows for the formation of an intermolecular hydrogen bond network between adjacent antibiotic molecules in the open channel configuration. Therefore, the extended conformation is expected to be the dominant conformer in an open AmB (or its amide derivatives) membrane channel. The derivative compounds for calculations were chosen according to their selective toxicity compared to AmB and they had a wide range of selective toxicity. Except for two AmB derivatives, the PES maps of the derivatives reveal that the molecules can coexist in more than one conformer. Taking into account the cumulative conclusions drawn from the earlier MD simulation studies of AmB membrane channel, the results of the potential energy surface maps, and the physical considerations of the molecular structures, we hypothesize a new model of structure-selective toxicity of AmB derivatives. In this proposed model the presence of the extended conformation as the only well defined global conformer for AmB derivatives is taken as the indicator of their higher selective toxicity. This model successfully explains our results. To further test our model, we also investigated an AmB derivative whose selective toxicity has not been experimentally measured before. Our prediction for the selective toxicity of this compound can be tested in experiments to validate or invalidate the proposed model.
  • Placeholder
    PublicationMetadata only
    Comparative molecular dynamics simulations of amphotericin B-cholesterol/ergosterol membrane channels
    (Elsevier, 2002) Baginski, Maciej; Borowski, Edward; Department of Physics; Reşat, Haluk; Faculty Member; Department of Physics; College of Sciences; N/A
    Amphotericin B (AmB) is a very effective anti-fungal polyene macrolide antibiotic whose usage is limited by its toxicity. Lack of a complete understanding of AmB's molecular mechanism has impeded attempts to design less toxic AmB derivatives. The antibiotic is known to interact with sterols present in the cell membrane to form ion channels that disrupt membrane function. The slightly higher affinity of AmB toward ergosterol (dominant sterol in fungal cells) than cholesterol (mammalian sterol) is regarded as the most essential factor on which antifungal chemotherapy is based. To study these differences at the molecular level, two realistic model membrane channels containing molecules of AmB, sterol (cholesterol or ergosterol), phospholipid, and water were studied by molecular dynamics (MID) simulations. Comparative analysis of the simulation data revealed that the sterol type has noticeable effect on the properties of AmB membrane channels. In addition to having a larger size, the AmB channel in the ergosterol-containing membrane has a more pronounced pattern of intermolecular hydrogen bonds. The interaction between the antibiotic and ergosterol is more specific than between the antibiotic and cholesterol. These observed differences suggest that the channel in the ergosterol-containing membrane is more stable and, due to its larger size, would have a higher ion conductance. These observations are in agreement with experiments. (C) 2002 Elsevier Science B.V. All rights reserved.
  • Placeholder
    PublicationMetadata only
    Enzyme-inhibitor association thermodynamics: explicit and continuum solvent studies
    (Cell Press, 1997) Marrone, Tami; McCammon, James Andrew; Department of Physics; Reşat, Haluk; Faculty Member; Department of Physics; College of Sciences; N/A
  • Placeholder
    PublicationMetadata only
    Cation transport properties of Amphotericin-B membrane channel
    (Biophysical Society, 1999) Baginski, Maciej; Department of Physics; Reşat, Haluk; Faculty Member; Department of Physics; College of Sciences; N/A
    N/A
  • Placeholder
    PublicationMetadata only
    A computational study of the reactivity of diethenylnaphthalenes towards anionic polymerization
    (Royal Soc Chemistry, 1999) Akın, Fatma Ahu; Erdem, Safiye Sağ; Nugay, Turgut; Aviyente, Viktorya; Department of Physics; Reşat, Haluk; Faculty Member; Department of Physics; College of Sciences; N/A
    Diethenyl, di(1-methylethenyl), and di(1-phenylethenyl) naphthalenes are known to be difunctional initiators used in the synthesis of thermoplastic elastomers. Semiempirical (AM1, PM3) and ab initio calculations (HF/6-31G, HF/6-31G*) have been carried out to determine the reactivity of these compounds towards anionic polymerization. For this purpose, geometrical parameters, electrostatic potentials, and frontier orbitals have been analyzed. Reaction paths starting from the diethenylnaphthalenes and reaching the proposed products have been studied, and transition structures along the paths have been located. The minimum energy conformers were determined through a conformational search around single bonds for a series of diethenylnaphthalenes. We have attempted to predict how the location of the vinyl groups affects the reactivity of diethenylnaphthalenes. Our results have revealed that the most suitable difunctional initiators for anionic polymerization are the compounds where the substituents lie away from the naphthalene bridge. We have also found that in some cases the substituents are conjugated with each other and di(1-phenylethenyl)naphthalenes are more reactive th an diethenylnaphthalenes which in turn are more reactive than di(1-methylethenyl)naphthalenes towards anionic polymerization.
  • Placeholder
    PublicationMetadata only
    Molecular properties of amphotericin b membrane channel: a molecular dynamics simulation
    (American Society for Pharmacology and Experimental Therapy, 1997) Baginski, Maciej; McCammon, J. Andrew; Department of Physics; Reşat, Haluk; Faculty Member; Department of Physics; College of Sciences; N/A
    Amphotericin B is a powerful but toxic antifungal antibiotic that is used to treat systemic infections. It forms ionic membrane channels in fungal cells. These antibiotic/sterol channels are responsible for the leakage of ions, which causes cell destruction. The detailed molecular properties and structure of amphotericin B channels are still unknown. In the current study, two molecular dynamic simulations were performed of a particular model of amphotericin B/cholesterol channel. The water and phospholipid environment were included in our simulations, and the results obtained were compared with available experimental data. It was found that it is mainly the hydrogen bonding interactions that keep the channel stable in its open form. Our study also revealed the important role of the intermolecular interactions among the hydroxyl, amino, and carboxyl groups of the channel-forming molecules; in particular, some hydroxyl groups stand out as new 'hot spots' that are potentially useful for chemotherapeutic investigations. Our results also help to clarify why certain antibiotic derivatives, with a blocked amino group, are less active. We present a hypothesis for the role of membrane lipids and cholesterol in the channel.
  • Placeholder
    PublicationMetadata only
    HIV protease solvation
    (Cell Press, 1997) Marrone, Tami; Hodge, Nicholas; McCammon, Andrew; Department of Physics; Reşat, Haluk; Faculty Member; Department of Physics; College of Sciences; N/A
  • Placeholder
    PublicationMetadata only
    Grand canonical ensemble Monte Carlo simulation of the dCpG/Proflavine crystal hydrate
    (Biophysical Society, 1996) Mezei, Mihaly; Department of Physics; Reşat, Haluk; Faculty Member; Department of Physics; College of Sciences; N/A
    The grand canonical ensemble Monte Carlo molecular simulation method is used to investigate hydration patterns in the crystal hydrate structure of the dCpG/proflavine intercalated complex. The objective of this study is to show by example that the recently advocated grand canonical ensemble simulation is a computationally efficient method for determining the positions of the hydrating water molecules in protein and nucleic acid structures. A detailed molecular simulation convergence analysis and an analogous comparison of the theoretical results with experiments clearly show that the grand ensemble simulations can be far more advantageous than the comparable canonical ensemble simulations.