Folding & design最新文献

{"title":"Transmuting α helices and β sheets","authors":"Seema Dalal ,&nbsp;Suganthi Balasubramanian ,&nbsp;Lynne Regan","doi":"10.1016/S1359-0278(97)00036-9","DOIUrl":"10.1016/S1359-0278(97)00036-9","url":null,"abstract":"<div><p>Protein architecture involves two main secondary structural classes: <em>α</em> helices and <em>β</em> sheets. Some natural proteins alter their fold in response to changes in solution conditions or as a consequence of mutation. Here, we discuss recent attempts to induce such conformational changes by design: specifically, the motivation and success of efforts to change one protein fold into a different one in response to the ‘Paracelsus Challenge’. The results of such efforts may provide a better understanding of the processes that underlie conformational plasticity in proteins.</p></div>","PeriodicalId":79488,"journal":{"name":"Folding & design","volume":"2 5","pages":"Pages R71-R79"},"PeriodicalIF":0.0,"publicationDate":"1997-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S1359-0278(97)00036-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20307625","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}

{"title":"Paper alert","authors":"Lynne Regan ,&nbsp;Luis Serrano ,&nbsp;Andrej Šali ,&nbsp;Amnon Horovitz ,&nbsp;Charles Wilson","doi":"10.1016/S1359-0278(97)00044-8","DOIUrl":"https://doi.org/10.1016/S1359-0278(97)00044-8","url":null,"abstract":"","PeriodicalId":79488,"journal":{"name":"Folding & design","volume":"2 5","pages":"Pages R81-R84"},"PeriodicalIF":0.0,"publicationDate":"1997-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S1359-0278(97)00044-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"137397632","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}

{"title":"Recovery of protein structure from contact maps","authors":"Michele Vendruscolo ,&nbsp;Edo Kussell ,&nbsp;Eytan Domany","doi":"10.1016/S1359-0278(97)00041-2","DOIUrl":"10.1016/S1359-0278(97)00041-2","url":null,"abstract":"<div><p><strong>Background:</strong> Prediction of a protein's structure from its amino acid sequence is a key issue in molecular biology. While dynamics, performed in the space of two-dimensional contact maps, eases the necessary conformational search, it may also lead to maps that do not correspond to any real three-dimensional structure. To remedy this, an efficient procedure is needed to reconstruct three-dimensional conformations from their contact maps.</p><p><strong>Results:</strong> We present an efficient algorithm to recover the three-dimensional structure of a protein from its contact map representation. We show that when a physically realizable map is used as target, our method generates a structure whose contact map is essentially similar to the target. Furthermore, the reconstructed and original structures are similar up to the resolution of the contact map representation. Next, we use nonphysical target maps, obtained by corrupting a physical one; in this case, our method essentially recovers the underlying physical map and structure. Hence, our algorithm will help to fold proteins, using dynamics in the space of contact maps. Finally, we investigate the manner in which the quality of the recovered structure degrades when the number of contacts is reduced.</p><p><strong>Conclusions:</strong> The procedure is capable of assigning quickly and reliably a three-dimensional structure to a given contact map. It is well suited for use in parallel with dynamics in contact map space to project a contact map onto its closest physically allowed structural counterpart.</p></div>","PeriodicalId":79488,"journal":{"name":"Folding & design","volume":"2 5","pages":"Pages 295-306"},"PeriodicalIF":0.0,"publicationDate":"1997-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S1359-0278(97)00041-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20309511","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}

{"title":"Similarities and differences between nonhomologous proteins with similar folds: evaluation of threading strategies","authors":"Baohong Zhang ,&nbsp;Lukasz Jaroszewski ,&nbsp;Leszek Rychlewski ,&nbsp;Adam Godzik","doi":"10.1016/S1359-0278(97)00042-4","DOIUrl":"10.1016/S1359-0278(97)00042-4","url":null,"abstract":"<div><p><strong>Background:</strong> There are many pairs and groups of proteins with similar folds and interaction patterns, but whose sequence similarity is below the threshold of easily recognizable sequence homology. The existence of multiple sequence solutions for a given fold has inspired fold prediction methods in which structural information from one protein is used to estimate the energy of another, putatively similar, structure.</p><p><strong>Results:</strong> A set of 68 pairs of proteins with similar folds and sequence identity in the 8–30% range is identified from the literature. For each pair, the energy of one protein, calculated using knowledge-based statistical potentials, is compared to the estimated energy, calculated with the same potentials but using the structural information (burial status and interaction pattern) of another protein with the same fold. Different energy estimates, corresponding to approximations used in various fold recognition algorithms, are calculated and compared to each other, as well as to the correct energy. It is shown that the local energy terms, based on burial and secondary structure preferences, can be reliably estimated with an accuracy close to 70%. At the same time, the two-body nonlocal energy loses over 60% of its value due to the repacking of the structure. Further approximations, such as the ‘frozen approximation’, can bring it to an essentially random value.</p><p><strong>Conclusions:</strong> Local energy terms could be used safely to improve fold recognition algorithms. To utilize pair interaction information, specially designed pair potentials and/or a self-consistent description of pair interactions is necessary.</p></div>","PeriodicalId":79488,"journal":{"name":"Folding & design","volume":"2 5","pages":"Pages 307-317"},"PeriodicalIF":0.0,"publicationDate":"1997-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S1359-0278(97)00042-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20309512","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}

{"title":"Simultaneous and coupled energy optimization of homologous proteins: a new tool for structure prediction","authors":"Chen Keasar ,&nbsp;Ron Elber ,&nbsp;Jeffrey Skolnick","doi":"10.1016/S1359-0278(97)00033-3","DOIUrl":"10.1016/S1359-0278(97)00033-3","url":null,"abstract":"<div><p><strong>Background:</strong> Homology-based modeling and global optimization of energy are two complementary approaches to prediction of protein structures. A combination of the two approaches is proposed in which a novel component is added to the energy and forces similarity between homologous proteins.</p><p><strong>Results:</strong> The combination was tested for two families: pancreatic hormones and homeodomains. The simulated lowest-energy structure of the pancreatic hormones is a reasonable approximation to the native fold. The lowest-energy structure of the homeodomains has 80% of the native contacts, but the helices are not packed correctly. The fourth lowest energy structure of the homeodomains has the correct helix packing (RMS 5.4 Å and 82% of the correct contacts). Optimizations of a single protein of the family yield considerably worse structures.</p><p><strong>Conclusions:</strong> Use of coupled homologous proteins in the search for the native fold is more successful than the folding of a single protein in the family.</p></div>","PeriodicalId":79488,"journal":{"name":"Folding & design","volume":"2 4","pages":"Pages 247-259"},"PeriodicalIF":0.0,"publicationDate":"1997-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S1359-0278(97)00033-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20212518","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}

{"title":"Local interactions in a Schellman motif dictate interhelical arrangement in a protein fragment","authors":"Muppalla Sukumar ,&nbsp;Lila M Gierasch","doi":"10.1016/S1359-0278(97)00030-8","DOIUrl":"10.1016/S1359-0278(97)00030-8","url":null,"abstract":"<div><p><strong>Background:</strong> As an approach to understanding the role of local sequence in determining protein tertiary structure, we have examined the conformation of a 23-residue peptide fragment corresponding to the structurally conserved helix–Schellman motif–helix (H–Sm–H) domain (residues 10–32) of cellular retinoic acid binding protein, along with variants designed to probe the contributions of the helix-terminating Gly23 and the hydrophobic interactions between Leu19 and Val24 in stabilizing the Schellman motif and hence helix termination.</p><p><strong>Results:</strong> In aqueous solution, NMR data for the H–Sm–H peptide show that it samples a largely helical conformation with a break in the helix at the point of the turn in the protein. The data also establish the presence of local hydrophobic interactions and intramolecular hydrogen bonds characteristic of a Schellman motif. Absence of helix termination in trifluoroethanol, a solvent known to disrupt hydrophobic interactions, along with an analysis of H<em>α</em> chemical shifts and NOEs in the variant peptides, suggest a major role for glycine in terminating the helix, with local hydrophobic interactions further stabilizing the Schellman motif.</p><p><strong>Conclusions:</strong> The presence of a Schellman motif in this isolated fragment in water is governed by local interactions and specifies the interspatial arrangement of the helices. This observation underlines the structure predictive value of folding motifs. As proposed for a Schellman motif, helix termination in this fragment is dictated by the local distribution of polar/apolar residues, which is reminiscent of the binary code for protein folding.</p></div>","PeriodicalId":79488,"journal":{"name":"Folding & design","volume":"2 4","pages":"Pages 211-222"},"PeriodicalIF":0.0,"publicationDate":"1997-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S1359-0278(97)00030-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20212515","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}

{"title":"Real-time NMR investigations of triple-helix folding and collagen folding diseases","authors":"Jean Baum ,&nbsp;Barbara Brodsky","doi":"10.1016/S1359-0278(97)00028-X","DOIUrl":"10.1016/S1359-0278(97)00028-X","url":null,"abstract":"<div><p>Folding of the collagen triple helix provides an opportunity to look at multichain molecular assembly. This triple helix also offers unique advantages for the study of folding because the process is very slow compared to globular proteins, and the kinetics of folding can be obtained in real time by NMR. Studies on triple-helical peptides illustrate the ability to observe kinetic folding intermediates directly and the ability to propose detailed mechanisms of folding through the use of real-time NMR methods. Defective collagen folding has been implicated in various connective tissue diseases and the capacity of NMR to look at the folding of specific sites provides a tool for obtaining information about altered folding mechanisms. Comparison of folding in peptides that model normal and diseased collagens could shed light on the molecular perturbation and the etiology of disease.</p></div>","PeriodicalId":79488,"journal":{"name":"Folding & design","volume":"2 4","pages":"Pages R53-R60"},"PeriodicalIF":0.0,"publicationDate":"1997-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S1359-0278(97)00028-X","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20212513","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}

{"title":"Cell dynamics of folding in two-dimensional model proteins","authors":"Marek Cieplak ,&nbsp;Jayanth R Banavar","doi":"10.1016/S1359-0278(97)00032-1","DOIUrl":"10.1016/S1359-0278(97)00032-1","url":null,"abstract":"<div><p><strong>Background:</strong> Functionally useful proteins are sequences of amino acids that fold rapidly under appropriate conditions into their native states. It is believed that rapid folders are sequences for which the folding dynamics entail the exploration of restricted conformations – the phase space can be thought of as a folding funnel. While there are many experimentally accessible predictions pertaining to the existence of such funnels and a coherent picture of the kinetics of folding has begun to emerge, there have been relatively few simple studies in the controlled setting of well-characterized lattice models.</p><p><strong>Results:</strong> We design rapidly folding sequences by assigning the strongest couplings to the contacts present in a target native state in a two-dimensional model of heteropolymers. Such sequences have large folding transition temperatures and low glass transition temperatures. The dependence of median folding times on temperature is investigated. The pathways to folding and their dependence on the temperature are illustrated via a study of the cell dynamics – a mapping of the dynamics into motion within the space of the maximally compact cells.</p><p><strong>Conclusions:</strong> Folding funnels can be defined operationally in a coarse-grained sense by mapping the states of the system into maximally compact conformations and then by identifying significant connectivities between them.</p></div>","PeriodicalId":79488,"journal":{"name":"Folding & design","volume":"2 4","pages":"Pages 235-245"},"PeriodicalIF":0.0,"publicationDate":"1997-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S1359-0278(97)00032-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20212517","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}

{"title":"Discrete representations of the protein Cα chain","authors":"Xavier F de la Cruz ,&nbsp;Michael W Mahoney ,&nbsp;Byungkook Lee","doi":"10.1016/S1359-0278(97)00031-X","DOIUrl":"10.1016/S1359-0278(97)00031-X","url":null,"abstract":"<div><p><strong>Background:</strong> When a large number of protein conformations are generated and screened, as in protein structure prediction studies, it is often advantageous to change the conformation in units of four consecutive residues at a time. The internal geometry of a chain of four consecutive C_<em>α</em> atoms is completely described by means of the three angles <em>θ</em>1, <em>τ</em>, and <em>θ</em>2, where <em>τ</em> is the virtual torsion angle defined by the four atoms and <em>θ</em>1 and <em>θ</em>2 are the virtual bond angles flanking the torsion angle on either side. In this paper, we examine the quality of the protein structures that can be obtained when they are represented by means of a set of discrete values for these angles (discrete states).</p><p><strong>Results:</strong> Different models were produced by selecting various different discrete states. The performance of these models was tested by rebuilding the C_<em>α</em> chains of 139 high-resolution nonhomologous protein structures using the build-up procedure of Park and Levitt. We find that the discrete state models introduce distortions at three levels, which can be measured by means of the ‘context-free’, ‘in-context’, and the overall root-mean-square deviation of the C_<em>α</em> coordinates (crms), respectively, and we find that these different levels of distortions are interrelated. As found by Park and Levitt, the overall crms decreases smoothly for most models with the complexity of the model. However, the decrease is significantly faster with our models than observed by Park and Levitt with their models. We also find that it is possible to choose models that perform considerably worse than expected from this smooth dependence on complexity.</p><p><strong>Conclusions:</strong> Of our models, the most suitable for use in initial protein folding studies appears to be model S8, in which the effective number of states available for a given residue quartet is 6.5. This model builds helices, <em>β</em>-strands, and coil/loop structures with approximately equal quality and gives the overall crms value of 1.9 Å on average with relatively little variation among the different proteins tried.</p></div>","PeriodicalId":79488,"journal":{"name":"Folding & design","volume":"2 4","pages":"Pages 223-234"},"PeriodicalIF":0.0,"publicationDate":"1997-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S1359-0278(97)00031-X","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20212516","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}

{"title":"Paper alert","authors":"Lynne Regan ,&nbsp;Luis Serrano ,&nbsp;Andrej Sˇali ,&nbsp;Amnon Horovitz ,&nbsp;Charles Wilson","doi":"10.1016/S1359-0278(97)00034-5","DOIUrl":"https://doi.org/10.1016/S1359-0278(97)00034-5","url":null,"abstract":"","PeriodicalId":79488,"journal":{"name":"Folding & design","volume":"2 4","pages":"Pages R61-R64"},"PeriodicalIF":0.0,"publicationDate":"1997-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S1359-0278(97)00034-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"137085279","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}