Proteins: Structure, Function and Bioinformatics
1097-0134
0887-3585
Mỹ
Cơ quản chủ quản: WILEY , Wiley-Liss Inc.
Lĩnh vực:
Molecular BiologyStructural BiologyBiochemistry
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Thông tin về tạp chí
PROTEINS : Structure, Function, and Bioinformatics publishes original reports of significant experimental and analytic research in all areas of protein research: structure, function, computation, genetics, and design. The journal encourages reports that present new experimental or computational approaches for interpreting and understanding data from biophysical chemistry, structural studies of proteins and macromolecular assemblies, alterations of protein structure and function engineered through techniques of molecular biology and genetics, functional analyses under physiologic conditions, as well as the interactions of proteins with receptors, nucleic acids, or other specific ligands or substrates. Research in protein and peptide biochemistry directed toward synthesizing or characterizing molecules that simulate aspects of the activity of proteins, or that act as inhibitors of protein function, is also within the scope of PROTEINS. In addition to full-length reports, short communications (usually not more than 4 printed pages) and prediction reports are welcome. Reviews are typically by invitation; authors are encouraged to submit proposed topics for consideration.
Các bài báo tiêu biểu
Structure of Met‐enkephalin in explicit aqueous solution using replica exchange molecular dynamics Abstract Replica exchange molecular dynamics (MD) simulations of Met‐enkephalin in explicit solvent reveal helical and nonhelical structures. Four predominant structures of Met‐enkephalin are sampled with comparable probabilities (two helical and two nonhelical). The energy barriers between these configurations are low, suggesting that Met‐enkephalin switches easily between configurations. This is consistent with the requirement that Met‐enkephalin be sufficiently flexible to bind to several different receptors. Replica exchange simulations of 32 ns are shown to sample approximately five times more configurational space than constant temperature MD simulations of the same duration. The energy landscape for the replica exchange simulation is presented. A detailed study of replica trajectories demonstrates that the significant increases in temperature provided by the replica exchange technique enable transitions from nonhelical to helical structures that would otherwise be prevented by kinetic trapping. Met‐enkephalin (Type Entrez Proteins; Value A61445; Service Entrez Proteins) Proteins 2002;46:225–234. Published 2001 Wiley‐Liss, Inc.
Tập 46 Số 2 - Trang 225-234 - 2002
The architecture of the binding site in redox protein complexes: Implications for fast dissociation Abstract Interprotein electron transfer is characterized by protein interactions on the millisecond time scale. Such transient encounters are ensured by extremely high rates of complex dissociation. Computational analysis of the available crystal structures of redox protein complexes reveals features of the binding site that favor fast dissociation. In particular, the complex interface is shown to have low geometric complementarity and poor packing. These features are consistent with the necessity for fast dissociation since the absence of close packing facilitates solvation of the interface and disruption of the complex. Proteins 2004;55:000–000. © 2004 Wiley‐Liss, Inc.
Tập 55 Số 3 - Trang 603-612 - 2004
Host‐guest scale of left‐handed polyproline II helix formation Abstract Despite the clear importance of the left‐handed polyproline II (PPII) helical conformation in many physiologically important processes as well as its potential significance in protein unfolded states, little is known about the physical determinants of this conformation. We present here a scale of relative PPII helix‐forming propensities measured for all residues, except tyrosine and tryptophan, in a proline‐based host peptide system. Proline has the highest measured propensity in this system, a result of strong steric interactions that occur between adjacent prolyl rings. The other measured propensities are consistent with backbone solvation being an important component in PPII helix formation. Side chain to backbone hydrogen bonding may also play a role in stabilizing this conformation. The PPII helix‐forming propensity scale will prove useful in future studies of the conformational properties of proline‐rich sequences as well as provide insights into the prevalence of PPII helices in protein unfolded states. Proteins 2003. © 2003 Wiley‐Liss, Inc.
Tập 53 Số 1 - Trang 68-75 - 2003
Unfolded state of polyalanine is a segmented polyproline II helix Abstract Definition of the unfolded state of proteins is essential for understanding their stability and folding on biological timescales. Here, we find that under near physiological conditions the configurational ensemble of the unfolded state of the simplest protein structure, polyalanine α‐helix, cannot be described by the commonly used Flory random coil model, in which configurational probabilities are derived from conformational preferences of individual residues. We utilize novel effectively ergodic sampling algorithms in the presence of explicit aqueous solvation, and observe water‐mediated formation of polyproline II helical (PII ) structure in the natively unfolded state of polyalanine, and its facilitation of α‐helix formation in longer peptides. The segmented PII helical coil preorganizes the unfolded state ensemble for folding pathway entry by reducing the conformational space available to the diffusive search. Thus, as much as half of the folding search in polyalanine is accomplished by preorganization of the unfolded state. Proteins 2004. © 2004 Wiley‐Liss, Inc.
Tập 55 Số 3 - Trang 493-501 - 2004
A tetrapeptide‐based method for polyproline II‐type secondary structure prediction Abstract We describe a new method for polyproline II‐type (PPII) secondary structure prediction based on tetrapeptide conformation properties using data obtained from all globular proteins in the Protein Data Bank (PDB). This is the first method for PPII prediction with a relatively high level of accuracy (∼60%). Our method uses only frequencies of different conformations among oligopeptides without any additional parameters. We also attempted to predict α‐helices and β‐strands using the same approach. We find that the application of our method reveals interrelation between sequence and structure even for very short oligopeptides (tetrapeptides). Proteins 2005. © 2005 Wiley‐Liss, Inc.
Tập 61 Số 4 - Trang 763-768 - 2005
A hierarchical approach to all‐atom protein loop prediction Abstract The application of all‐atom force fields (and explicit or implicit solvent models) to protein homology‐modeling tasks such as side‐chain and loop prediction remains challenging both because of the expense of the individual energy calculations and because of the difficulty of sampling the rugged all‐atom energy surface. Here we address this challenge for the problem of loop prediction through the development of numerous new algorithms, with an emphasis on multiscale and hierarchical techniques. As a first step in evaluating the performance of our loop prediction algorithm, we have applied it to the problem of reconstructing loops in native structures; we also explicitly include crystal packing to provide a fair comparison with crystal structures. In brief, large numbers of loops are generated by using a dihedral angle‐based buildup procedure followed by iterative cycles of clustering, side‐chain optimization, and complete energy minimization of selected loop structures. We evaluate this method by using the largest test set yet used for validation of a loop prediction method, with a total of 833 loops ranging from 4 to 12 residues in length. Average/median backbone root‐mean‐square deviations (RMSDs) to the native structures (superimposing the body of the protein, not the loop itself) are 0.42/0.24 Å for 5 residue loops, 1.00/0.44 Å for 8 residue loops, and 2.47/1.83 Å for 11 residue loops. Median RMSDs are substantially lower than the averages because of a small number of outliers; the causes of these failures are examined in some detail, and many can be attributed to errors in assignment of protonation states of titratable residues, omission of ligands from the simulation, and, in a few cases, probable errors in the experimentally determined structures. When these obvious problems in the data sets are filtered out, average RMSDs to the native structures improve to 0.43 Å for 5 residue loops, 0.84 Å for 8 residue loops, and 1.63 Å for 11 residue loops. In the vast majority of cases, the method locates energy minima that are lower than or equal to that of the minimized native loop, thus indicating that sampling rarely limits prediction accuracy. The overall results are, to our knowledge, the best reported to date, and we attribute this success to the combination of an accurate all‐atom energy function, efficient methods for loop buildup and side‐chain optimization, and, especially for the longer loops, the hierarchical refinement protocol. Proteins 2004;55:000–000. © 2004 Wiley‐Liss, Inc.
Tập 55 Số 2 - Trang 351-367 - 2004
Refinement of protein structures in explicit solvent Abstract We present a CPU efficient protocol for refinement of protein structures in a thin layer of explicit solvent and energy parameters with completely revised dihedral angle terms. Our approach is suitable for protein structures determined by theoretical (e.g., homology modeling or threading) or experimental methods (e.g., NMR). In contrast to other recently proposed refinement protocols, we put a strong emphasis on consistency with widely accepted covalent parameters and computational efficiency. We illustrate the method for NMR structure calculations of three proteins: interleukin‐4, ubiquitin, and crambin. We show a comparison of their structure ensembles before and after refinement in water with and without a force field energy term for the dihedral angles; crambin was also refined in DMSO. Our results demonstrate the significant improvement of structure quality by a short refinement in a thin layer of solvent. Further, they show that a dihedral angle energy term in the force field is beneficial for structure calculation and refinement. We discuss the optimal weight for the energy constant for the backbone angle omega and include an extensive discussion of meaning and relevance of the calculated validation criteria, in particular root mean square Z scores for covalent parameters such as bond lengths. Proteins 2003;50:496–506. © 2003 Wiley‐Liss, Inc.
Tập 50 Số 3 - Trang 496-506 - 2003
Implicit flexibility in protein docking: Cross‐docking and local refinement Abstract In previous CAPRI rounds (3–5) we showed that using MD‐generated ensembles, as inputs for a rigid‐body docking algorithm, increased our success rate, especially for targets exhibiting substantial amounts of induced fit. In recent rounds (6–11), our cross‐docking was followed by a short MD‐based local refinement for the subset of solutions with the lowest interaction energies after minimization. The above approach showed promising results for target 20, where we were able to recover 30% of native contacts for one of our submitted models. Further tests, performed a posteriori, revealed that cross‐docking approach produces more near‐native (NN) solutions but only for targets with large conformational changes upon binding. However, at the time of the blind docking experiment, these improved solutions were not chosen for the subsequent refinement, as their interaction energies after minimization ranked poorly compared with other solutions. This indicates deficiencies in the present scoring schemes that are based on interaction energies of minimized structures. Refinement MD simulations substantially increase the fraction of native contacts for NN docked solutions, but generally worsen interface and ligand RMSD. Further analysis shows that although MD simulations are able to improve sidechain packing across the interface, which results in an increased fraction of native contacts, they are not capable of improving interface and ligand backbone RMSD for NN structures beyond 1.5 and 3.5 Å, respectively, even if explicit solvent is used. Proteins 2007. © 2007 Wiley‐Liss, Inc.
Tập 69 Số 4 - Trang 750-757 - 2007
Docking unbound proteins using shape complementarity, desolvation, and electrostatics Abstract A comprehensive docking study was performed on 27 distinct protein‐protein complexes. For 13 test systems, docking was performed with the unbound X‐ray structures of both the receptor and the ligand. For the remaining systems, the unbound X‐ray structure of only molecule was available; therefore the bound structure for the other molecule was used. Our method optimizes desolvation, shape complementarity, and electrostatics using a Fast Fourier Transform algorithm. A global search in the rotational and translational space without any knowledge of the binding sites was performed for all proteins except nine antibodies recognizing antigens. For these antibodies, we docked their well‐characterized binding site—the complementarity‐determining region defined without information of the antigen—to the entire surface of the antigen. For 24 systems, we were able to find near‐native ligand orientations (interface Cα root mean square deviation less than 2.5 Å from the crystal complex) among the top 2,000 choices. For three systems, our algorithm could identify the correct complex structure unambiguously. For 13 other complexes, we either ranked a near‐native structure in the top 20 or obtained 20 or more near‐native structures in the top 2,000 or both. The key feature of our algorithm is the use of target functions that are highly tolerant to conformational changes upon binding. If combined with a post‐processing method, our algorithm may provide a general solution to the unbound docking problem. Our program, called ZDOCK, is freely available to academic users (http://zlab.bu.edu/∼rong/dock/ ). Proteins 2002;47:281–294. © 2002 Wiley‐Liss, Inc.
Tập 47 Số 3 - Trang 281-294 - 2002