Folding & design最新文献_第6页

What's new in protein folding? EMBO Workshop: Protein folding and misfolding inside and outside the cell 蛋白质折叠有什么新发现?EMBO工作坊:细胞内外的蛋白质折叠和错误折叠

Folding & design Pub Date : 1998-06-01 DOI: 10.1016/S1359-0278(98)00022-4

Sheena E Radford

引用次数: 2

Optimizing energy potentials for success in protein tertiary structure prediction 优化能势，成功预测蛋白质三级结构

Folding & design Pub Date : 1998-06-01 DOI: 10.1016/S1359-0278(98)00030-3

Ting-Lan Chiu , Richard A Goldstein

{"title":"Optimizing energy potentials for success in protein tertiary structure prediction","authors":"Ting-Lan Chiu , Richard A Goldstein","doi":"10.1016/S1359-0278(98)00030-3","DOIUrl":"10.1016/S1359-0278(98)00030-3","url":null,"abstract":"<div>Background: Success in solving the protein structure prediction problem relies on the choice of an accurate potential energy function. For a single protein sequence, it has been shown that the potential energy function can be optimized for predictive success by maximizing the energy gap between the correct structure and the ensemble of random structures relative to the distribution of the energies of these random structures (the Z-score). Different methods have been described for implementing this procedure for an ensemble of database proteins. Here, we demonstrate a new approach.Results: For a single protein sequence, the probability of success (i.e. the probability that the folded state is the lowest energy state) is derived. We then maximize the average probability of success for a set of proteins to obtain the optimal potential energy function. This results in maximum attention being focused on the proteins whose structures are difficult but not impossible to predict.Conclusions: Using a lattice model of proteins, we show that the optimal interaction potentials obtained by our method are both more accurate and more likely to produce successful predictions than those obtained by other averaging procedures.</div>","PeriodicalId":79488,"journal":{"name":"Folding & design","volume":"3 3","pages":"Pages 223-228"},"PeriodicalIF":0.0,"publicationDate":"1998-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S1359-0278(98)00030-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20587728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 36

Models of protein interactions: how to choose one 蛋白质相互作用的模型:如何选择一个

Folding & design Pub Date : 1998-06-01 DOI: 10.1016/S1359-0278(98)00028-5

Rose Du , Alexander Yu Grosberg , Toyoichi Tanaka

{"title":"Models of protein interactions: how to choose one","authors":"Rose Du , Alexander Yu Grosberg , Toyoichi Tanaka","doi":"10.1016/S1359-0278(98)00028-5","DOIUrl":"10.1016/S1359-0278(98)00028-5","url":null,"abstract":"<div>Background: There have been many attempts to approximate realistic protein interaction energies by coarse graining (i.e. considering interactions between amino acids rather than those between atoms). In particular, many 20-letter models have been derived (corresponding to the 20 naturally occurring amino acids). Because such models remain computationally infeasible, many two-letter models have been proposed as further simplifications. The choice of which model to use remains arbitrary, however. In this work, we formulate the framework within which the quality of approximate interaction potentials with respect to folding can be defined explicitly.Results: Using a recently proposed criterion for comparing interaction matrices, we compare various 20 × 20 interaction matrices and obtain the two-letter model that most closely approximates each 20 × 20 matrix. We find that there are considerable differences among the 20 × 20 matrices. In particular, some matrices are much more similar to the hydrophobic model than others. Furthermore, we find that although the best two-letter approximation of a 20-letter model is a significantly better approximation than a random two-letter model, it is still a poor approximation of realistic protein interactions.Conclusions: The determination of the best two-letter approximations of various 20-letter models of protein interaction energies reveals the degree to which hydrophobic interactions dominate in each of the models and hence in proteins.</div>","PeriodicalId":79488,"journal":{"name":"Folding & design","volume":"3 3","pages":"Pages 203-211"},"PeriodicalIF":0.0,"publicationDate":"1998-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S1359-0278(98)00028-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20483364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 13

Paper alert 纸警报

Folding & design Pub Date : 1998-06-01 DOI: 10.1016/S1359-0278(98)00031-5

Lynne Regan , Andrej Šali , Amnon Horovitz , Jane Clarke , Francois Major

引用次数: 0

Protein hydration and unfolding – insights from experimental partial specific volumes and unfolded protein models 蛋白质水合作用和展开-从实验部分比体积和未折叠蛋白质模型的见解

Folding & design Pub Date : 1998-04-01 DOI: 10.1016/S1359-0278(98)00016-9

Lynne Reed Murphy , Nobuyuki Matubayasi , Vilia A Payne , Ronald M Levy

{"title":"Protein hydration and unfolding – insights from experimental partial specific volumes and unfolded protein models","authors":"Lynne Reed Murphy , Nobuyuki Matubayasi , Vilia A Payne , Ronald M Levy","doi":"10.1016/S1359-0278(98)00016-9","DOIUrl":"10.1016/S1359-0278(98)00016-9","url":null,"abstract":"<div>Background: The partial specific volume of a protein is an experimental quantity containing information about solute–solvent interactions and protein hydration. We use a hydration-shell model to partition the partial specific volume into an intrinsic volume occupied by the protein and a change in the volume occupied by the solvent resulting from the solvent interactions with the protein. We seek to extract microscopic information about protein hydration and unfolding from experimental volume measurements without using computer simulations. We employ the idea that the protein–solvent interaction will be proportional to the surface area of the protein.Results: A linear relationship is obtained when the difference between the experimental protein partial specific volume and its intrinsic volume is plotted as a function of the protein solvent-accessible surface area. The effect of using different protein volume definitions on the analysis of protein volumetric properties is discussed. Volumetric data are used to test a model for the unfolded state of proteins and to make predictions about the denatured state.Conclusions: The linear relationship between hydration-shell volume change and accessible surface area reflects the similar surface properties (fractional composition of nonpolar, polar and charged surface) among a diverse set of proteins. This linear relationship is found to be independent of how the solution is partitioned into solute and solvent components. The interpretation of hydration shell versus bulk water properties is found to be very model dependent, however. The maximally exposed unfolded protein model is found to be inconsistent with experimental volume changes of unfolding.</div>","PeriodicalId":79488,"journal":{"name":"Folding & design","volume":"3 2","pages":"Pages 105-118"},"PeriodicalIF":0.0,"publicationDate":"1998-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S1359-0278(98)00016-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20486327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 82

Reading protein sequences backwards 反向读取蛋白质序列

Folding & design Pub Date : 1998-04-01 DOI: 10.1016/S1359-0278(98)00013-3

Emmanuel Lacroix , Ana Rosa Viguera , Luis Serrano

{"title":"Reading protein sequences backwards","authors":"Emmanuel Lacroix , Ana Rosa Viguera , Luis Serrano","doi":"10.1016/S1359-0278(98)00013-3","DOIUrl":"10.1016/S1359-0278(98)00013-3","url":null,"abstract":"<div>Background: Reading a protein sequence backwards provides a new polypeptide that does not align with its parent sequence. The foldability of this new sequence is questionable. On one hand, structure prediction at low resolution using lattice simulations for such a protein provided a model close to the native parent fold or to a topological mirror image of it. On the other hand, there is no experimental evidence yet to tell whether such a retro protein folds (and to which structure) or not.Results: In this work, we have analysed the possibility of a retro protein folding in two different ways. First, we modelled the retro sequence of the α-spectrin SH3 domain through distance geometry and molecular dynamics. This contradicted the plausibility of a mirror image of the native domain, whereas basic considerations opposed the likelihood of the native fold. Second, we obtained experimental evidence that the retro sequences of the SH3 domain, as well as the B domain of Staphylococcal protein A and the B1 domain of Streptococcal protein G, are unfolded proteins, even though some propensities for the formation of secondary structures might remain.Conclusions: Retro proteins are no more similar to their parent sequences than any random sequence despite their common hydrophobic/hydrophilic pattern, global amino acid composition and possible tertiary contacts. Although simple folding models contribute to our global understanding of protein folding, they cannot yet be used to predict the structure of new proteins.</div>","PeriodicalId":79488,"journal":{"name":"Folding & design","volume":"3 2","pages":"Pages 79-85"},"PeriodicalIF":0.0,"publicationDate":"1998-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S1359-0278(98)00013-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20487054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 39

Tolerance of a protein helix to multiple alanine and valine substitutions 蛋白质螺旋对多个丙氨酸和缬氨酸取代的耐受性

Folding & design Pub Date : 1998-04-01 DOI: 10.1016/S1359-0278(98)00017-0

Lydia M Gregoret , Robert T Sauer

{"title":"Tolerance of a protein helix to multiple alanine and valine substitutions","authors":"Lydia M Gregoret , Robert T Sauer","doi":"10.1016/S1359-0278(98)00017-0","DOIUrl":"10.1016/S1359-0278(98)00017-0","url":null,"abstract":"<div>Background: Protein stability is influenced by the intrinsic secondary structure propensities of the amino acids and by tertiary interactions, but which of these factors dominates is not known in most cases. We have used combinatorial mutagenesis to examine the effects of substituting a good helix-forming residue (alanine) and a poor helix-forming residue (valine) at many positions in an α helix of a native protein. This has allowed us to average over many molecular environments and assess to what extent the results reflect intrinsic helical propensities or are masked by tertiary effects.Results: Alanine or valine residues were combinatorially substituted at 12 positions in α-helix 1 of λ repressor. Functional proteins were selected and sequenced to determine the degree to which each residue type was tolerated. On average, valine substitutions were accommodated slightly less well than alanine substitutions. On a positional basis, however, valine was tolerated as well as alanine at the majority of sites. In fact, alanine was preferred over valine statistically significantly only at four sites. Studies of mutant protein and peptide stabilities suggest that tertiary interactions mask the intrinsic secondary structure propensity differences at most of the remaining residue positions in this α helix.Conclusions: At the majority of positions in α-helix 1 of λ repressor, tertiary interactions with other parts of the protein can be viewed as an environmental ‘buffer’ that help to diminish the helix destabilizing effects of valine mutations and allow these mutations to be tolerated at frequencies similar to alanine mutations.</div>","PeriodicalId":79488,"journal":{"name":"Folding & design","volume":"3 2","pages":"Pages 119-126"},"PeriodicalIF":0.0,"publicationDate":"1998-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S1359-0278(98)00017-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20486328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 46

Cooperativity in protein folding: from lattice models with sidechains to real proteins 蛋白质折叠中的协同性:从带侧链的晶格模型到真实的蛋白质

Folding & design Pub Date : 1998-04-01 DOI: 10.1016/S1359-0278(98)00018-2

DK Klimov , D Thirumalai

{"title":"Cooperativity in protein folding: from lattice models with sidechains to real proteins","authors":"DK Klimov , D Thirumalai","doi":"10.1016/S1359-0278(98)00018-2","DOIUrl":"10.1016/S1359-0278(98)00018-2","url":null,"abstract":"<div>Background: Over the past few years novel folding mechanisms of globular proteins have been proposed using minimal lattice and off-lattice models. The factors determining the cooperativity of folding in these models and especially their explicit relation to experiments have not been fully established, however.Results: We consider equilibrium folding transitions in lattice models with and without sidechains. A dimensionless measure, Ωc, is introduced to quantitatively assess the degree of cooperativity in lattice models and in real proteins. We show that larger values of Ωc resembling the values seen in proteins are obtained in lattice models with sidechains. The enhanced cooperativity of such models results from possible denser packing of sidechains in the interior of the model polypeptide chain. We also establish that Ωc correlates extremely well with σT = (Tθ – Tf)/Tθ, where Tθ and Tf are collapse and folding transition temperatures, respectively. These theoretical ideas are used to analyze folding transitions in two-state folders (RNase A, chymotrypsin inhibitor 2, fibronectin type III modules and tendamistat) and three-state folders (apomyoglobin and lysozyme). The values of Ωc extracted from experiments show a correlation with σT (suitably generalized when folding is induced by denaturants or acid).Conclusions: A quantitative description of the cooperative transition of real proteins can be made by lattice models with sidechains. The degree of cooperativity in minimal models and real proteins can be expressed in terms of the single parameter σ, which can be estimated from experimental data.</div>","PeriodicalId":79488,"journal":{"name":"Folding & design","volume":"3 2","pages":"Pages 127-139"},"PeriodicalIF":0.0,"publicationDate":"1998-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S1359-0278(98)00018-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20486329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 107

Folding rate dependence on the chain length for RNA-like heteropolymers 类rna异聚物的折叠速率与链长的关系

Folding & design Pub Date : 1998-04-01 DOI: 10.1016/S1359-0278(98)00012-1

Oxana V Galzitskaya , Alexei V Finkelstein

{"title":"Folding rate dependence on the chain length for RNA-like heteropolymers","authors":"Oxana V Galzitskaya , Alexei V Finkelstein","doi":"10.1016/S1359-0278(98)00012-1","DOIUrl":"10.1016/S1359-0278(98)00012-1","url":null,"abstract":"<div>Background: Computer experiments and analytical estimates have shown that protein and RNA chains can reach their most stable folds without an exhaustive search over all their possible conformations. Protein-like chain folding proceeds via a specific nucleus and under conditions optimal for the fastest folding of these chains the dependence of the folding time (t) on the chain length (L) is in accord with the power law t ∼ Lb (b is a constant).Results: Using Monte-Carlo folding simulations for a simple model of RNA secondary structure formation, we estimate the RNA chain length dependence of the time necessary to reach the lowest energy fold. Our results are compatible with a relatively weak power dependence of the folding time on the chain length, t ∼ Lb. Such dependencies have been observed for different folding conditions, both for random sequences (here, b > 5) and for sequences edited to stabilize their lowest energy folds (for extremely edited sequences, b < 2). Although folding transitions in RNA chains are not an all-or-none type in terms of thermodynamics, they proceed via a folding nucleus in terms of kinetics. The peculiarity (compared with protein folding) is that the RNA critical nucleus is big and non-specific.Conclusions: We have obtained a general scaling for the dependence of the RNA secondary structure on the chain length. The obtained power dependence is very weak compared with an exponential dependence for an exhaustive sorting.</div>","PeriodicalId":79488,"journal":{"name":"Folding & design","volume":"3 2","pages":"Pages 69-78"},"PeriodicalIF":0.0,"publicationDate":"1998-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S1359-0278(98)00012-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20487053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 10

Coupling protein stability and protein function in Escherichia coli CspA 大肠杆菌CspA偶联蛋白稳定性及蛋白功能研究

Folding & design Pub Date : 1998-04-01 DOI: 10.1016/S1359-0278(98)00014-5

Brian J Hillier , Hector M Rodriguez , Lydia M Gregoret

引用次数: 75