The Experts below are selected from a list of 315 Experts worldwide ranked by ideXlab platform
Mark A. Ratner - One of the best experts on this subject based on the ideXlab platform.
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all atom numerical studies of self assembly of zwitterionic peptide amphiphiles
Journal of Physical Chemistry B, 2004Co-Authors: Stefan Tsonchev, George C Schatz, Alessandro Troisi, Mark A. RatnerAbstract:We present an approach to study the self-assembly of organic macromolecules, based on all-atom empirical force field calculations. The approach is applied to self-assemblies of zwitterionic peptide amphiphiles possessing large dipoles in their hydrophilic headgroups. The assembly is built from the bottom up by first optimizing the diad amphiphile, which is then used as a basic unit to subsequently first build quartets, and then 4 × 4 supercells of molecules to be studied in periodic boundary conditions. Explicit water solvent is added to the surface of the periodic structures and molecular dynamics simulations are performed on them. The calculations reveal an interesting structure of the resulting assemblies: the dipoles in the upper parts of the headgroups are aligned in an antiParallel fashion with respect to each other and along one of the periodic axes, while hydrogen bonds in the lower, rigid parts of the headgroups form a Parallel beta sheet along the same direction. It is shown that the structure ...
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on the structure and stability of self assembled zwitterionic peptide amphiphiles a theoretical study
Nano Letters, 2004Co-Authors: Stefan Tsonchev, George C Schatz, Alessandro Troisi, Mark A. RatnerAbstract:The structures of self-assembled peptide amphiphiles are studied using empirical force fields and atomistic molecular dynamics calculations. The hydrophilic headgroups of these amphiphiles possess a lower, rigid part and an upper, flexible part. At an appropriate pH large dipoles are found in the flexible part of the headgroups, leading to attractive interactions between them, while the rigid parts participate in the formation of an effective Parallel beta sheet due to hydrogen bonding oriented in the same direction as the large dipoles, and stabilizing the self-assembly in that direction. Molecular dynamics simulations on the self-assembled amphiphiles are performed with periodic boundary conditions in two dimensions. The tendency of the nanostructure to curve around an axis Parallel to the dipoles and the beta sheet is revealed by removing the periodic boundary conditions, one direction at a time, leading to the conclusion that a cylindrical micelle would be the most stable one.
Elsa C Y Yan - One of the best experts on this subject based on the ideXlab platform.
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Chiral Sum Frequency Generation Spectroscopy Provides a Set of Optical Vibrational Markers to Distinguish Protein Secondary Structures at Interfaces
Biophysical Journal, 2011Co-Authors: Elsa C Y YanAbstract:Quantitative characterization of protein secondary structures at surfaces is important in biological and biomedical sciences. However, probing secondary structures and their changes at surfaces remains technically challenging. We applied chiral sum frequency generation (SFG) spectroscopy to analyze secondary structures at interfaces. We identified a set of vibrational optical markers to distinguish random coils, alpha-helices, and Beta-Sheets. We found that a monolayer of alpha-helical proteins, including rhodopsin and alamethicin, yields chiral vibrational signals at 3280-3350 cm−1 corresponding to the N-H stretch of the peptide backbones, which are not detected from random coils and Beta-Sheets. We also observed the chiral amide I stretch from amyloid aggregates formed by islet amyloid polypeptide (IAPP) at 1620−1 cm, a vibrational signature for Parallel Beta-Sheet distinct from that for anti-Parallel Beta-Sheet at 1630 cm−1. We combined these results with our observations that random coils are silent in chiral SFG spectra and derived a set of markers that allow identification of secondary structures. We further used these markers to investigate the misfolding of IAPP at the lipid/water interface and observed the conversion of IAPP from random-coil to alpha-helical structures followed by Parallel Beta-Sheets in the time scale of hours upon interaction with lipid membranes. Our results demonstrate that chiral SFG spectroscopy allows not only characterization of static structures, but also investigations of kinetics. Because chiral SFG spectroscopy is insensitive to achiral solvent, it is relatively background-free. As a second-order optical method, it provides vibrational signals in the visible region for easy detection. These characteristics combined with intrinsic surface selectivity make chiral SFG spectroscopy complementary to other vibrational methods in studies of protein conformational changes and ultrafast vibrational dynamics for solving fundamental and engineering problems at the molecular level.
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in situ misfolding of human islet amyloid polypeptide at interfaces probed by vibrational sum frequency generation
Journal of the American Chemical Society, 2010Co-Authors: Elsa C Y YanAbstract:Kinetic analysis of conformational changes of proteins at interfaces is crucial for understanding many biological processes at membrane surfaces. In this study, we demonstrate that surface-selective sum frequency generation (SFG) spectroscopy can be used to investigate kinetics of conformational changes of proteins at interfaces. We focus on an intrinsically disordered protein, human islet amyloid polypeptide (hIAPP) that is known to misfold into the Beta-Sheet structure upon interaction with membranes. Using the ssp polarization setting (s-polarized SFG, s-polarized visible, and p-polarized infrared), we observe changes in the amide I spectra of hIAPP at the air/water interface after addition of dipalmitoylphosphoglycerol (DPPG) that correspond to the lipid-induced changes in secondary structures. We also used the chiral-sensitive psp polarization setting to obtain amide I spectra and observed a gradual buildup of the chiral structures that display the vibrational characteristics of Parallel Beta-Sheets. We speculate that the second-order chiral-optical response at the antisymmetric stretch frequency of Parallel Beta-Sheet at 1622 cm(-1) could be a highly characteristic optical property of the Beta-Sheet aggregates not only for hIAPP, but possibly also for other amyloid proteins. Analyzing the achiral and chiral amide I spectra, we conclude that DPPG induces the misfolding of hIAPP from alpha-helical and random-coil structures to the Parallel Beta-Sheet structure at the air/water interface. We propose that SFG could complement existing techniques in obtaining kinetic and structural information for probing structures and functions of proteins at interfaces.
Stefan Tsonchev - One of the best experts on this subject based on the ideXlab platform.
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all atom numerical studies of self assembly of zwitterionic peptide amphiphiles
Journal of Physical Chemistry B, 2004Co-Authors: Stefan Tsonchev, George C Schatz, Alessandro Troisi, Mark A. RatnerAbstract:We present an approach to study the self-assembly of organic macromolecules, based on all-atom empirical force field calculations. The approach is applied to self-assemblies of zwitterionic peptide amphiphiles possessing large dipoles in their hydrophilic headgroups. The assembly is built from the bottom up by first optimizing the diad amphiphile, which is then used as a basic unit to subsequently first build quartets, and then 4 × 4 supercells of molecules to be studied in periodic boundary conditions. Explicit water solvent is added to the surface of the periodic structures and molecular dynamics simulations are performed on them. The calculations reveal an interesting structure of the resulting assemblies: the dipoles in the upper parts of the headgroups are aligned in an antiParallel fashion with respect to each other and along one of the periodic axes, while hydrogen bonds in the lower, rigid parts of the headgroups form a Parallel beta sheet along the same direction. It is shown that the structure ...
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on the structure and stability of self assembled zwitterionic peptide amphiphiles a theoretical study
Nano Letters, 2004Co-Authors: Stefan Tsonchev, George C Schatz, Alessandro Troisi, Mark A. RatnerAbstract:The structures of self-assembled peptide amphiphiles are studied using empirical force fields and atomistic molecular dynamics calculations. The hydrophilic headgroups of these amphiphiles possess a lower, rigid part and an upper, flexible part. At an appropriate pH large dipoles are found in the flexible part of the headgroups, leading to attractive interactions between them, while the rigid parts participate in the formation of an effective Parallel beta sheet due to hydrogen bonding oriented in the same direction as the large dipoles, and stabilizing the self-assembly in that direction. Molecular dynamics simulations on the self-assembled amphiphiles are performed with periodic boundary conditions in two dimensions. The tendency of the nanostructure to curve around an axis Parallel to the dipoles and the beta sheet is revealed by removing the periodic boundary conditions, one direction at a time, leading to the conclusion that a cylindrical micelle would be the most stable one.
Paul Francis Alewood - One of the best experts on this subject based on the ideXlab platform.
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Solution structure of a defensin-like peptide from platypus venom.
Biochemical Journal, 1999Co-Authors: Allan M. Torres, Dianne Alewood, Paul Francis Alewood, Xiu-hong Wang, Jamie I. Fletcher, Ross Smith, Richard J. Simpson, Graham M. Nicholson, Struan Sutherland, Cliff H. GallagherAbstract:Three defensin-like peptides (DLPs) were isolated from platypus venom and sequenced. One of these peptides, DLP-1, was synthesized chemically and its three-dimensional structure was determined using NMR spectroscopy. The main structural elements of this 42-residue peptide were an anti-Parallel Beta-Sheet comprising residues 15-18 and 37-40 and a small 3(10) helix spanning residues 10-12. The overall three-dimensional fold is similar to that of beta-defensin-12, and similar to the sodium-channel neurotoxin ShI (Stichodactyla helianthus neurotoxin I). However, the side chains known to be functionally important in beta-defensin-12 and ShI are not conserved in DLP-1, suggesting that it has a different biological function. Consistent with this contention, we showed that DLP-1 possesses no anti-microbial properties and has no observable activity on rat dorsal-root-ganglion sodium-channel currents.
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Solution structure of robustoxin, the lethal neurotoxin from the funnel-web spider Atrax robustus.
FEBS letters, 1997Co-Authors: Paul K Pallaghy, Dianne Alewood, Paul Francis Alewood, Raymond S. NortonAbstract:The solution structure of robustoxin, the lethal neurotoxin from the Sydney funnel-web spider Atrax robustus, has been determined from 2D 1H NMR data. Robustoxin is a polypeptide of 42 residues cross-linked by four disulphide bonds, the connectivities of which were determined from NMR data and trial structure calculations to be 1-15, 8-20, 14-31 and 16-42 (a 1-4/2-6/3-7/5-8 pattern). The structure consists of a small three-stranded, anti-Parallel Beta-Sheet and a series of interlocking gamma-turns at the C-terminus. It also contains a cystine knot, thus placing it in the inhibitor cystine knot motif family of structures, which includes the omega-conotoxins and a number of plant and animal toxins and protease inhibitors. Robustoxin contains three distinct charged patches on its surface, and an extended loop that includes several aromatic and non-polar residues. Both of these structural features may play a role in its binding to the voltage-gated sodium channel.
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Solution structure of robustoxin, the lethal neurotoxin from the funnel-web spider Atrax robustus
'Elsevier BV', 1997Co-Authors: Paul K Pallaghy, Paul Francis Alewood, Alewood D, Rs NortonAbstract:The solution structure of robustoxin, the lethal neurotoxin from the Sydney funnel-web spider Atrax robustus, has been determined from 2D H-1 NMR data, Robustoxin is a polypeptide of 42 residues cross-linked by four disulphide bonds, the connectivities of which were determined from NMR data and trial structure calculations to be 1-15, 8-20, 14-31 and 16-42 (a 1-4/2-6/3-7/5-8 pattern), The structure consists of a small three-stranded, anti-Parallel Beta-Sheet and a series of interlocking gamma-turns at the C-terminus. It also contains a cystine knot, thus placing it in the inhibitor cystine knot motif family of structures, which includes the omega-conotoxins and a number of plant and animal toxins and protease inhibitors. Robustoxin contains three distinct charged patches on its surface, and an extended loop that includes several aromatic and non-polar residues, Both of these structural features may play a role in its binding to the voltage-gated sodium channel. (C) 1997 Federation of European Biochemical Societies
Raymond S. Norton - One of the best experts on this subject based on the ideXlab platform.
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Solution structure of robustoxin, the lethal neurotoxin from the funnel-web spider Atrax robustus.
FEBS letters, 1997Co-Authors: Paul K Pallaghy, Dianne Alewood, Paul Francis Alewood, Raymond S. NortonAbstract:The solution structure of robustoxin, the lethal neurotoxin from the Sydney funnel-web spider Atrax robustus, has been determined from 2D 1H NMR data. Robustoxin is a polypeptide of 42 residues cross-linked by four disulphide bonds, the connectivities of which were determined from NMR data and trial structure calculations to be 1-15, 8-20, 14-31 and 16-42 (a 1-4/2-6/3-7/5-8 pattern). The structure consists of a small three-stranded, anti-Parallel Beta-Sheet and a series of interlocking gamma-turns at the C-terminus. It also contains a cystine knot, thus placing it in the inhibitor cystine knot motif family of structures, which includes the omega-conotoxins and a number of plant and animal toxins and protease inhibitors. Robustoxin contains three distinct charged patches on its surface, and an extended loop that includes several aromatic and non-polar residues. Both of these structural features may play a role in its binding to the voltage-gated sodium channel.
