Current Protein & Peptide Science[JOURNAL]
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168 papers
Miniaturized hemoproteins.
Nastri F, Lombardi A, D'Andrea LD … +3 more , Sanseverino M, Maglio O, Pavone V
Biopolymers · 1998 · PMID 9692324 · Publisher ↗
The present paper highlights and reviews current research in the field of hemoprotein models. Hemoproteins have been extensively studied in order to understand structure-function relationships, and to design new molecule...
The present paper highlights and reviews current research in the field of hemoprotein models. Hemoproteins have been extensively studied in order to understand structure-function relationships, and to design new molecules with desired functions. A wide number of synthetic analogues have been developed, using quite different approaches. They differ in molecular structures, ranging from simple meso-substituted tetraaryl-metalloporphyrins and peptide-porphyrin conjugates. In this paper we summarize the state of the art on peptide based hemoprotein models. We also report here the approach used by us to develop a new class of molecules, named mimochromes. They can be regarded as miniaturized hemoproteins, because mimochromes are low molecular weight compounds with some structural and functional properties common to those of the parent high molecular weight protein. The basic structure of mimochromes is a deuteroporphyrin ring covalently linked to two helical peptide chains. Two molecules of this series have been fully characterized. All the information derived from their structural analysis has been applied to the design of new analogues with additional functions.
Local control of peptide conformation: stabilization of cis proline peptide bonds by aromatic proline interactions.
Wu WJ, Raleigh DP
Biopolymers · 1998 Apr · PMID 9530015 · Publisher ↗
In the native state of proteins there is a marked tendency for an aromatic amino acid to precede a cis proline. There are also significant differences between the three aromatic amino acids with Tyr exhibiting a noticeab...
In the native state of proteins there is a marked tendency for an aromatic amino acid to precede a cis proline. There are also significant differences between the three aromatic amino acids with Tyr exhibiting a noticeably higher propensity than Phe or Trp to precede a cis proline residue. In order to study the role that local interactions play in these conformation preferences, a set of tetrapeptides of the general sequence acetyl-Gly-X-Pro-Gly-carboxamide (GXPG), where X = Tyr, Phe, Trp, Ala, or cyclohexyl alanine, were synthesized and studied by nmr. Analysis of the nmr data shows that none of the peptides adopt a specific backbone structure. Ring current shifts, the equilibrium constant, the Van't Hoff enthalpy, and the measured rate of cis-trans isomerization all indicate that the cis proline conformer is stabilized by favorable interactions between the aromatic ring and the proline residue. Analysis of the side chain conformation of the aromatic residue and analysis of the chemical shifts of the pyrrolidine ring protons shows that the aromatic side chain adopts a preferred conformation in the cis form. The distribution of rotamers and the effect of an aromatic residue on the cis-trans equilibrium indicate that the preferred conformation is populated to approximately 62% for the Phe containing peptide, 67% for the Tyr containing peptide, and between 75 and 80% for the Trp containing peptide. The interaction is unaffected by the addition of 8M urea. These local interactions favor an aromatic residue immediately preceding a cis proline, but they cannot explain the relative propensities for Phe-Pro, Tyr-Pro, and Trp-Pro cis peptide bonds observed in the native state of proteins. In the model peptides the percentage of the cis proline conformer is 21% GYPG while it is 17% for GFPG. This difference is considerably smaller than the almost three to one preponderance observed for cis Tyr-Pro peptide bonds vs cis Phe-Pro peptide bonds in the protein database.
CD conformational studies on synthetic peptides encompassing the processing domain of the ocytocin/neurophysin precursor.
Simonetti M, Falcigno L, Paolillo L … +1 more , Di Bello C
Biopolymers · 1997 Apr · PMID 9080781 · Publisher ↗
Synthetic peptides of different size, reproducing the proteolytic processing site of proocytocin, were studied by CD under several experimental conditions in order to ascertain the ability of different solvents to stabil...
Synthetic peptides of different size, reproducing the proteolytic processing site of proocytocin, were studied by CD under several experimental conditions in order to ascertain the ability of different solvents to stabilize secondary structural motifs, such as alpha-helix tracts and beta-turns. A combination of deconvolution methods and empirical calculations subtracting the contributions due to unordered structures from the spectra suggests that in solution (a) mainly two distinct families of ordered conformers containing structurally different beta-turns are present, (b) the relative stability of the different conformers depends from the nature of the solvent, and (c) in the case of the larger peptides, a population containing an alpha-helical conformation is also present. From the biological point of view the presence of at least two families of ordered conformers could be in line with current theories assuming that the catalytic effect of the receptor microenvironment may be determinant in shifting the equilibrium toward the active conformation.
Calculations of the CD spectrum of bovine pancreatic ribonuclease.
Kurapkat G, Krüger P, Wollmer A … +6 more , Fleischhauer J, Kramer B, Zobel E, Koslowski A, Botterweck H, Woody RW
Biopolymers · 1997 Mar · PMID 9057494 · Publisher ↗
CD spectra of bovine pancreatic ribonuclease A (RNase A) and its subtilisin-modified from (RNase S) have been calculated, based upon high-resolution structures from x-ray diffraction. All known transitions in the peptide...
CD spectra of bovine pancreatic ribonuclease A (RNase A) and its subtilisin-modified from (RNase S) have been calculated, based upon high-resolution structures from x-ray diffraction. All known transitions in the peptide and side-chain groups, especially the aromatic and disulfide groups, have been included. Calculations have been performed with both the matrix method and with first-order perturbation theory. A newly developed method for treating the electrostatic interactions among transition charge densities and between static charge distributions and transition charge densities is used. The effects of local electrostatic fields upon the group transition energies are included for all transitions. Rotational strengths generated by the matrix method were combined with Gaussian band shapes to generate theoretical CD spectra. The calculated spectra reproduce the signs and approximate magnitudes of the near-uv CD bands of both RNase A and S. Agreement is most satisfactory for the negative 275 nm band, dominated by tyrosine contributions. In agreement with two previous studies by other workers, coupling between Tyr 73 and Tyr 115 is the single most important factor in this band. The positive band observed near 240 nm is dominated by disulfide contributions, according to our results. The far-uv CD spectrum is poorly reproduced by the calculations. The observed 208 nm band, characteristic of alpha-helices, is absent from the calculated spectrum, probably because the helices in RNase are short. A strong positive couplet centered near 190 nm is predicted but not observed. Possible reasons for these incorrect predictions of the current theoretical model in the far-uv are discussed.
Progress in the design of DNA sequence-specific lexitropsins.
Walker WL, Kopka ML, Goodsell DS
Biopolymers · 1997 · PMID 9782774 · Publisher ↗
Sequence-specific polyamides that bind in the minor groove of DNA are attractive candidates for antibiotics, cancer chemotherapeutics, and transcriptional antagonists. This paper reviews the progress of structure-based d...
Sequence-specific polyamides that bind in the minor groove of DNA are attractive candidates for antibiotics, cancer chemotherapeutics, and transcriptional antagonists. This paper reviews the progress of structure-based design of minor-groove-binding polyamides, from the first structure of netropsin with DNA, to the effective linked polyamides currently under study. A theory of polyamide specificity is also reviewed, introducing methods to determine the optimal strategies for targeting a given DNA sequence within a genome of competing sequences.
Peptide binding and antigen presentation by class II histocompatibility glycoproteins.
Jensen PE
Biopolymers · 1997 · PMID 9316394 · Publisher ↗
The immune system has evolved complex mechanisms for the recognition and elimination of pathogens. CD4+ helper T lymphocytes play a central role in orchestrating immune responses and their activation is carefully regulat...
The immune system has evolved complex mechanisms for the recognition and elimination of pathogens. CD4+ helper T lymphocytes play a central role in orchestrating immune responses and their activation is carefully regulated. These cells selectively recognize short peptide antigens stably associated with membrane-bound class II histocompatibility glycoproteins that are selectively expressed in specialized antigen presenting cells. The class II-peptide complexes are generated through a series of events that occur in membrane-bound compartments within antigen presenting cells that, collectively, have become known as the class II antigen processing pathway. In the present paper, our current understanding of this pathway is reviewed with emphasis on mechanisms that regulate peptide binding by class II histocompatibility molecules.
Peptide binding by class I and class II MHC molecules.
Batalia MA, Collins EJ
Biopolymers · 1997 · PMID 9316393 · Publisher ↗
Major histocompatibility complex (MHC) antigens bind peptides of diverse sequences with high affinity. They do this in order to generate maximal immunological protection by covering the spectrum of peptides that may be s...
Major histocompatibility complex (MHC) antigens bind peptides of diverse sequences with high affinity. They do this in order to generate maximal immunological protection by covering the spectrum of peptides that may be seen by a host over the course of its lifetime. However, in many circumstances the immune system does not recognize a particular peptide that it should for maximum advantage over the pathogen. In other situations, the immune system goes awry and incorrectly recognizes a self-peptide that it should not. This results in disease characterized by recognition and attack of self. Rheumatoid arthritis is an example of just such a disease. In either of these situations, peptide-based modalities for immune therapy would be an advantage. However, peptide-based therapies require a thorough understanding of the forces involved in peptide binding. Great strides have been made in elucidating the mechanisms by which these MHC proteins may bind peptides with diverse sequences and high affinity. This review summarizes the current data obtained from crystallographic analyses of peptide binding for both class I and class II MHC molecules. Unfortunately, as yet these data have not allowed us to predict which peptides will bind with high affinity to a specific MHC molecule.
Farnesyltransferase as a target for anticancer drug design.
Qian Y, Sebti SM, Hamilton AD
Biopolymers · 1997 · PMID 9174410 · Publisher ↗
The currently understood function for Ras in signal transduction is in mediating the transmission of signals from external growth factors to the cell nucleus. Mutated forms of this GTP-binding protein are found in 30% of...
The currently understood function for Ras in signal transduction is in mediating the transmission of signals from external growth factors to the cell nucleus. Mutated forms of this GTP-binding protein are found in 30% of human cancers with particularly high prevalence in colon and pancreatic carcinomas. These mutations destroy the GTPase activity of Ras and cause the protein to be locked in its active, GTP bound form. As a result, the signaling pathways are activated, leading to uncontrolled tumor growth. Ras function in signaling requires its association with the plasma membrane. This is achieved by posttranslational farnesylation of a cysteine residue present as part of the CA1A2X carboxyl terminal tetrapeptide of all Ras proteins. The enzyme that recognizes and farnesylates the CA1A2X sequence, Ras farnesyltransferase (FTase), has become an important target for the design of inhibitors that might be interesting as antitumor agents. Several approaches have been taken in the search for in vivo active inhibitors of farnesyltransferase. These include the identification of natural products such as the chaetomellic and zaragozic acids that mimic farnesylpyrophosphate, bisubstrate transition state analogs combining elements of the farnesyl and tetrapeptide substrates and peptidomimetics that reproduce features of the carboxyl terminal tetrapeptide CA1A2X sequence. This last group of compounds has been most successful in showing highly potent inhibition of FTase and selective blocking of Ras processing in a range of Ras transformed tumor cell lines at concentrations as low as 10 nM. Certain peptidomimetics will also block tumor growth in various mouse models, with apparently few toxic side effects. These results suggest that farnesyltransferase inhibitors hold considerable promise as anticancer drugs in the clinic.
Computational study of packing a collagen-like molecule: quasi-hexagonal vs "Smith" collagen microfibril model.
Lee J, Scheraga HA, Rackovsky S
Biopolymers · 1996 · PMID 9140199 · Publisher ↗
The lateral packing of a collagen-like molecule, CH3CO-(Gly-L-Pro-L-Pro)4-NHCH3, has been examined by energy minimization with the ECEPP/3 force field. Two current packing models, the Smith collagen microfibril twisted e...
The lateral packing of a collagen-like molecule, CH3CO-(Gly-L-Pro-L-Pro)4-NHCH3, has been examined by energy minimization with the ECEPP/3 force field. Two current packing models, the Smith collagen microfibril twisted equilateral pentagonal model and the quasi-hexagonal packing model, have been extensively investigated. In treating the Smith microfibril model, energy minimization was carried out on various conformations including those with the symmetry of equivalent packing, i.e., in which the triple helices were arranged equivalently with respect to each other. Both models are based on the experimental observation of the characteristic axial periodicity, D = 67 nm, of light and dark bands, indicating that, if any superstructure exists, it should consist of five triple helices. The quasi-hexagonal packing structure is found to be energetically more favorable than the Smith microfibril model by as much as 31.2 kcal/mol of five triple helices. This is because the quasi-hexagonal packing geometry provides more nonbonded interaction possibilities between triple helices than does the Smith microfibril geometry. Our results are consistent with recent x-ray studies with synthetic collagen-like molecules and rat tail tendon, in which the data were interpreted as being consistent with either a quasi-hexagonal or a square-triangular structure.
NMR and x-ray studies of collagen model peptides.
Mayo KH
Biopolymers · 1996 · PMID 8765607 · Publisher ↗
The main structural component in collagen is the triple helix which is generally composed of the amino acid sequence repeat (X-Y-Gly)n with proline and hydroxyproline often present at positions X and Y. Non-globular, fib...
The main structural component in collagen is the triple helix which is generally composed of the amino acid sequence repeat (X-Y-Gly)n with proline and hydroxyproline often present at positions X and Y. Non-globular, fibrillar proteins like most collagens are difficult to work with from a structural perspective. An alternative approach to collagen structural elucidation is to study considerably shorter fragments of the triple helix. To date, various triple helical model peptides such as (Pro-Pro-Gly)n and (Pro-Hyp-Gly)n have been investigated by various physical and spectroscopic techniques. The advent of easy solid phase peptide synthetic methodology and the development of multi-dimensional heteronuclear and high field NMR technologies have promoted significant advances in the structure elucidation of a number of triple helix peptides. Here, the main focus is to review and to address the current state of knowledge in the field of NMR and x-ray analysis of triple helical model peptides.
Exploration of compact protein conformations using the guided replication Monte Carlo method.
Solomon JE, Liney D
Biopolymers · 1995 Nov · PMID 7578950 · Publisher ↗
We have studied the use of a new Monte Carlo (MC) chain generation algorithm, introduced by T. Garel and H. Orland [(1990) Journal of Physics A, Vol. 23, pp. L621-L626], for examining the thermodynamics of protein foldin...
We have studied the use of a new Monte Carlo (MC) chain generation algorithm, introduced by T. Garel and H. Orland [(1990) Journal of Physics A, Vol. 23, pp. L621-L626], for examining the thermodynamics of protein folding transitions and for generating candidate C(alpha) backbone structures as starting points for a de novo protein structure paradigm. This algorithm, termed the guided replication Monte Carlo method, allows a rational approach to the introduction of known "native" folded characteristics as constraints in the chain generation process . We have shown this algorithm to be computationally very efficient in generating large ensembles of candidate C(alpha) chains on the face centered cubic lattice, and illustrate its use by calculating a number of thermodynamic quantities related to protein folding characteristics. In particular, we have used this static MC algorithm to compare such temperature-dependent quantities as the ensemble mean energy, ensemble mean free energy, the heat capacity, and the mean-square radius of gyration. We also demonstrate the use of several simple "guide fields" for introducing protein-specific constraints into the ensemble generation process. Several extensions to our current model are suggested, and applications of the method to other folding related problems are discussed.
Approach to discovering novel therapeutic agents for osteoporosis based on integrin receptor blockade.
Chorev M, Dresner-Pollak R, Eshel Y … +1 more , Rosenblatt M
Biopolymers · 1995 · PMID 8589242 · Publisher ↗
On a global scale, osteoporosis is a major and growing public health problem. In the United States, osteoporosis is present in 24 million people (mostly women) and contributes to more than 1.3 million fractures/year. Ser...
On a global scale, osteoporosis is a major and growing public health problem. In the United States, osteoporosis is present in 24 million people (mostly women) and contributes to more than 1.3 million fractures/year. Serious morbidity and mortality result from these fractures. Current therapies for osteoporosis are few, efficacy is limited, and side effects problematic. Fundamental to the pathophysiology of osteoporosis is an imbalance between the tightly coupled processes of bone resorption and bone formation that characterize normal bone remodeling. Our laboratory is engaged in a research effort focused on elucidating the role of the osteoclast integrin in bone resorption, defining the nature of ligand-integrin interactions, and developing antagonists for cell surface adhesion molecules, particularly the alpha v beta 3 vitronectin-like integrin receptor present on the surface of human osteoclasts. Peptides containing the internal arginine-glycine-aspartic acid (RGD) motif have been shown to inhibit osteoclast-mediated bone resorption in vivo. We are now designing more potent and selective inhibitors of bone resorption as a potential new mechanism-based therapeutic approach to osteoporosis based on a novel mechanism. In an effort to rapidly identify the highest affinity ligands for the human alpha v beta 3 integrin, we have generated combinatorial peptide libraries containing substantial structural diversity. For instance, based on all possible sequence combinations of extracellular matrix proteins known to bind alpha v beta 3, we recently synthesized and chemically analyzed a library of 360,000 peptides, all of which contain RGD.(ABSTRACT TRUNCATED AT 250 WORDS)
Overcrossing spectra of protein backbones: characterization of three-dimensional molecular shape and global structural homologies.
Arteca GA
Biopolymers · 1993 Dec · PMID 8268409 · Publisher ↗
A procedure is developed and applied to characterize the global shape and folding features of the backbone of a chain molecule. The methodology is based on the following concept: the probability of observing a rigid plac...
A procedure is developed and applied to characterize the global shape and folding features of the backbone of a chain molecule. The methodology is based on the following concept: the probability of observing a rigid placement of a backbone in 3-space as a projected curve with N overcrossings. The numerical computation of these probabilities allows one to construct the overcrossing spectrum of a macromolecule at a given configuration. Although the spectrum is built from the knowledge of the nuclear geometry of the main-chain atoms, the shape descriptor overlooks local geometrical features (such as distances and contacts) and provides a characterization of essential (topological) features of the overall fold, such as its compactness and degree of entanglement. In contrast with other shape descriptors, the present approach gives an absolute characterization of the configuration considered, and not one that is relative to an arbitrarily chosen reference structure. Moreover, it is possible to discriminate between folding features that otherwise may not be distinguished when using other geometrical or topological global descriptors. The overcrossing spectrum is proposed as a tool that complements current structural analyses of macromolecules, especially when monitoring structural homologies within a group of related or unrelated polymers. In this work, we apply the methodology to the analysis of proteins having the globin fold. The results are compared with those of other proteins exhibiting similar size and number of residues. Some basic properties of the spectra as a function of the chain length are also discussed.
NMR and computer-aided modeling studies of the interactions between a cyclic hexapeptide and the two enantiomers of some Boc- and Fmoc-amino acids.
McEwen I
Biopolymers · 1993 Jun · PMID 8318666 · Publisher ↗
The cyclic hexapeptide cyclo [-Pro1-Gly2-Glu3 (OBzl)-Pro4-Phe5-Leu6-] (1) was modeled and synthesized to be used for chiral discrimination studies. Total correlated spectroscopy and nuclear Overhauser effect spectroscopy...
The cyclic hexapeptide cyclo [-Pro1-Gly2-Glu3 (OBzl)-Pro4-Phe5-Leu6-] (1) was modeled and synthesized to be used for chiral discrimination studies. Total correlated spectroscopy and nuclear Overhauser effect spectroscopy spectra of the cyclic hexapeptide 1 in CDCl3 showed the presence of three stereoisomers: two dominant stereoisomers 1a and 1b that exchanged chemically with each other, and a minor stereoisomer 1c (4%) that exchanged exclusively with the stereoisomer 1b. Of the two dominant stereoisomers, only 1a interacted specifically with t-butyloxycarbonyl (Boc-) and 9-flourenylmethyloxycarbonyl (Fmoc-) amino acids in CDCl3. The interaction site of 1a when complexing with the derivatized amino acids was the chain segment Phe5-Leu6. The Phe5 NH and Leu6 NH protons are contiguous and solvent exposed. Their nmr signals shifted strongly downfield with the addition of Boc- or Fmoc- amino acids to the peptide solution. Thus, both NH protons hydrogen bond to the amino acids, forming a two-point hydrogen-bonding complex. The peptide stereoisomer 1b did not interact specifically with the Boc- and Fmoc-amino acids because of the lack of two contiguous and solvent-exposed peptidic NH protons that seem to be needed for specific interactions of the cyclic hexapeptide 1 with the Boc- and Fmoc-amino acids. A clear difference in the interaction of 1a with D- and L-enantiomers of Boc- Trp and Fmoc-Trp was observed with nmr spectroscopy. Docking models and molecular mechanics calculations together with nmr observations showed that the NH proton of the indole ring of the Boc-L-Trp and the Fmoc-L-Trp hydrogen bonded to the Pro1 carbonyl group. In this three-point hydrogen-bonding complex, the indole ring becomes locked underneath the Leu residue. The nmr signals of all the Leu6 protons (except for Leu NH) shifted strongly upfield owing to the shielding effect of the indole aromatic ring currents. The indole NH of the D-enantiomer did not hydrogen bond to the Pro1 carbonyl group because the formation of such a three-point hydrogen-bonding complex was thermodynamically unfavorable.
A method for studying the structure of uniaxially aligned biopolymers using solid state 15N-nmr: application to Bombyx mori silk fibroin fibers.
Nicholson LK, Asakura T, Demura M … +1 more , Cross TA
Biopolymers · 1993 May · PMID 8343580 · Publisher ↗
Recent advances in the application of solid state nmr spectroscopy to uniformly aligned biopolymers have opened a window through which to view the detailed structure of biological macromolecules that are unable to be see...
Recent advances in the application of solid state nmr spectroscopy to uniformly aligned biopolymers have opened a window through which to view the detailed structure of biological macromolecules that are unable to be seen with standard techniques for structure determination such as x-ray diffraction. Atomic resolution structural details are obtained from solid state nmr data in the form of bond orientations, which yield the relative positions of specific atoms within the molecule. For static aligned systems such as fibers, in which rapid reorientation about the axis of alignment does not occur, it has generally been necessary to perform trial and error line-shape simulations to extract structural details from nmr spectra arising from a single type of nuclear spin interaction. In the present work, a new method is developed in which solid state 15N-nmr spectra obtained from uniaxially aligned molecules placed with the axis of alignment both parallel and perpendicular to the magnetic field are analyzed to yield the orientations of specific molecular bonds. Analytical expressions are derived that utilize spectral features read from 15N chemical shift anisotropy line shapes to calculate a discrete number of possible orientations for a specific site. The 15N-1H dipolar interaction is employed to further narrow the number of unique orientations possible for a given site. With this method, a neighborhood of possible orientations is quickly determined, and full line-shape simulations within this region of allowed space can be performed to refine the limits of orientation. This technique demonstrates the use of a single type of isotopic label to determine the orientation of a specific molecular group such as a peptide plane within a protein. Results from the application of this method to the Bombyx mori silk fibroin protein provide structural detail that is consistent with currently accepted structural models based on fiber diffraction studies.
Excluded volume effects on the partition of single- and double-stranded oligodeoxynucleotides between two liquid phases.
Zimmerman SB, Murphy LD
Biopolymers · 1992 Oct · PMID 1420964 · Publisher ↗
The distribution coefficients of single- and double-stranded oligodeoxynucleotides in a PEG 8000/phosphate two-phase system are a function of their chain length. Values of the distribution coefficients are in general agr...
The distribution coefficients of single- and double-stranded oligodeoxynucleotides in a PEG 8000/phosphate two-phase system are a function of their chain length. Values of the distribution coefficients are in general agreement with a simple extension of a model for excluded volume effects (the "available volume model") which was applied previously to the distribution of proteins in this system. The current results therefore provide a second set of examples for molecules of very different geometry where the distribution added molecules is controlled by excluded volume interactions between those molecules and the PEG 8000 of the two-phase system.
Anti-insulin antibody structure and conformation. II. Molecular dynamics with explicit solvent.
Tanner JJ, Nell LJ, McCammon JA
Biopolymers · 1992 Jan · PMID 1617146 · Publisher ↗
Molecular dynamics at 300 K was used as a conformation searching tool to analyze a knowledge-based structure prediction of an anti-insulin antibody. Solvation effects were modeled by packing water molecules around the an...
Molecular dynamics at 300 K was used as a conformation searching tool to analyze a knowledge-based structure prediction of an anti-insulin antibody. Solvation effects were modeled by packing water molecules around the antigen binding loops. Some loops underwent backbone and side-chain conformational changes during the 95-ps equilibration, and most of these new, lower potential energy conformations were stable during the subsequent 200-ps simulation. Alterations to the model include changes in the intraloop, main-chain hydrogen bonding network of loop H3, and adjustments of Tyr and Lys side chains of H3 induced by hydrogen bonding to water molecules. The structures observed during molecular dynamics support the conclusion of the previous paper that hydrogen bonding will play the dominant role in antibody-insulin recognition. Determination of the structure of the antibody by x-ray crystallography is currently being pursued to provide an experimental test of these results. The simulation appears to improve the model, but longer simulations at higher temperatures should be performed.
Prediction of fluorine chemical shifts in proteins.
Gregory DH, Gerig JT
Biopolymers · 1991 Jun · PMID 1912343 · Publisher ↗
Molecular dynamics calculations have been used in an effort to estimate the change in fluorine nmr shielding when a fluorine nucleus enters the tertiary structure of a protein. Considerations of the possible interactions...
Molecular dynamics calculations have been used in an effort to estimate the change in fluorine nmr shielding when a fluorine nucleus enters the tertiary structure of a protein. Considerations of the possible interactions that can define the shift parameter change suggest that van der Waals interactions are the leading determinant of fluorine shifts in proteins, although aromatic ring currents, other magnetic anisotropies, and electrostatic field effects could result in shift distinctions of 1 ppm or smaller. Results of our studies of a fluorine-containing analogue of the ribonuclease A S-protein/S-peptide complex indicate that static structures such as those implied by crystallographic data lead to overestimates of the magnitude of the van der Waals shielding term; molecular dynamics simulations provide indications of the effects of conformational averaging in defining this term. The treatment used predicts the correct direction of the shift change when the fluorine enters this protein environment from aqueous solution and, with an experimentally supported choice of adjustable parameters, gives agreement with the magnitude of the shift.
Virtual rigid body dynamics.
Head-Gordon T, Brooks CL
Biopolymers · 1991 Jan · PMID 2025686 · Publisher ↗
An important direction in biological simulations is the development of methods that permit the study of larger systems and/or longer simulation time scales than is currently feasible by molecular dynamics. One such metho...
An important direction in biological simulations is the development of methods that permit the study of larger systems and/or longer simulation time scales than is currently feasible by molecular dynamics. One such method designed with this objective in mind is stochastic boundary molecular dynamics (SBMD). SBMD was developed for the characterization of spatially localized processes in proteins, and has been shown to successfully reproduce structural and dynamical properties of these macromolecules, as compared to a molecular dynamics control simulation, when concerted or global motions are not present. The virtual rigid body dynamics method presented in this work extends the range of applicability of the SBMD method, by providing a framework to include these important long time scale conformational transitions. In this paper we describe the two-step implementation of the virtual rigid body model: first, the reduction of the full atomic representation to a reduced particle (virtual bond) model, and second, the propagation of the dynamics of flexibly connected rigid bodies containing virtual atom sites.
Secondary-structure dependent chemical shifts in proteins.
Williamson MP
Biopolymers · 1990 Aug 15-Sep · PMID 2375792 · Publisher ↗
Chemical shift data have been collected on eight proteins that have the same conformation in solution as in their crystal structures. Ring-current shifts have been calculated and subtracted from the exerimentally measure...
Chemical shift data have been collected on eight proteins that have the same conformation in solution as in their crystal structures. Ring-current shifts have been calculated and subtracted from the exerimentally measured shifts, to leave shifts that depend only on local conformation. Overall, the shifts show an approximately normal distribution with no appreciable skewness, thus confirming that ring-current shifts have the overall effect of skewing the distribution to high field. In helices, NH and C(alpha)H have a high significant tendency to resonate to high field, whereas they resonate to low field in beta-sheets. Side-chain protons resonate slightly to high field in beta-sheets. Chemical shift distributions are narrowest for side-chain protons, and widest for amide protons. When only slowly exchanging amide protons are considered, the high field shift for amide protons in helices is more pronounced, but there is only a small difference in sheets. C(alpha)H signals at the N-terminal end of helices tend to resonate to higher field than those at the C-terminal end, whereas for NH signals it is the C-terminal end that resonates to higher field. There is no significant effect of position within the helix on side-chain signals, implying that the helix dipole has little effect on shifts within the helix.
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