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Deciphering the shape and deformation of secondary structures through local conformation analysis

Julie Baussand, Anne-Claude Camproux
<span title="">2011</span> <i title="Springer Nature"> <a target="_blank" rel="noopener" href="https://fatcat.wiki/container/m36qvjwuvnegpgzopqbhvg7k3e" style="color: black;">BMC Structural Biology</a> </i> &nbsp;
Protein deformation has been extensively analysed through global methods based on RMSD, torsion angles and Principal Components Analysis calculations. Here we use a local approach, able to distinguish among the different backbone conformations within loops, a-helices and b-strands, to address the question of secondary structures' shape variation within proteins and deformation at interface upon complexation. Results: Using a structural alphabet, we translated the 3 D structures of large sets of
more &raquo; ... protein-protein complexes into sequences of structural letters. The shape of the secondary structures can be assessed by the structural letters that modeled them in the structural sequences. The distribution analysis of the structural letters in the three protein compartments (surface, core and interface) reveals that secondary structures tend to adopt preferential conformations that differ among the compartments. The local description of secondary structures highlights that curved conformations are preferred on the surface while straight ones are preferred in the core. Interfaces display a mixture of local conformations either preferred in core or surface. The analysis of the structural letters transition occurring between protein-bound and unbound conformations shows that the deformation of secondary structure is tightly linked to the compartment preference of the local conformations. Conclusion: The conformation of secondary structures can be further analysed and detailed thanks to a structural alphabet which allows a better description of protein surface, core and interface in terms of secondary structures' shape and deformation. Induced-fit modification tendencies described here should be valuable information to identify and characterize regions under strong structural constraints for functional reasons.
<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1186/1472-6807-11-9">doi:10.1186/1472-6807-11-9</a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pubmed/21284872">pmid:21284872</a> <a target="_blank" rel="external noopener" href="https://pubmed.ncbi.nlm.nih.gov/PMC3224362/">pmcid:PMC3224362</a> <a target="_blank" rel="external noopener" href="https://fatcat.wiki/release/54m4p3jjszhslfgwwwcp4sqjam">fatcat:54m4p3jjszhslfgwwwcp4sqjam</a> </span>
<a target="_blank" rel="noopener" href="https://web.archive.org/web/20170829185550/https://bmcstructbiol.biomedcentral.com/track/pdf/10.1186/1472-6807-11-9?site=http://bmcstructbiol.biomedcentral.com" title="fulltext PDF download" data-goatcounter-click="serp-fulltext" data-goatcounter-title="serp-fulltext"> <button class="ui simple right pointing dropdown compact black labeled icon button serp-button"> <i class="icon ia-icon"></i> Web Archive [PDF] <div class="menu fulltext-thumbnail"> <img src="https://blobs.fatcat.wiki/thumbnail/pdf/5c/e0/5ce02d8f3d3b2fc0a7b6f834a4b6e6f30e171526.180px.jpg" alt="fulltext thumbnail" loading="lazy"> </div> </button> </a> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1186/1472-6807-11-9"> <button class="ui left aligned compact blue labeled icon button serp-button"> <i class="unlock alternate icon" style="background-color: #fb971f;"></i> springer.com </button> </a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3224362" title="pubmed link"> <button class="ui compact blue labeled icon button serp-button"> <i class="file alternate outline icon"></i> pubmed.gov </button> </a>

Mining protein loops using a structural alphabet and statistical exceptionality

Leslie Regad, Juliette Martin, Gregory Nuel, Anne-Claude Camproux
<span title="">2010</span> <i title="Springer Nature"> <a target="_blank" rel="noopener" href="https://fatcat.wiki/container/n5zrklrhlzhtdorf4rk4rmeo3i" style="color: black;">BMC Bioinformatics</a> </i> &nbsp;
Protein loops encompass 50% of protein residues in available three-dimensional structures. These regions are often involved in protein functions, e.g. binding site, catalytic pocket... However, the description of protein loops with conventional tools is an uneasy task. Regular secondary structures, helices and strands, have been widely studied whereas loops, because they are highly variable in terms of sequence and structure, are difficult to analyze. Due to data sparsity, long loops have
more &raquo; ... been systematically studied. Results: We developed a simple and accurate method that allows the description and analysis of the structures of short and long loops using structural motifs without restriction on loop length. This method is based on the structural alphabet HMM-SA. HMM-SA allows the simplification of a three-dimensional protein structure into a onedimensional string of states, where each state is a four-residue prototype fragment, called structural letter. The difficult task of the structural grouping of huge data sets is thus easily accomplished by handling structural letter strings as in conventional protein sequence analysis. We systematically extracted all seven-residue fragments in a bank of 93000 protein loops and grouped them according to the structural-letter sequence, named structural word. This approach permits a systematic analysis of loops of all sizes since we consider the structural motifs of seven residues rather than complete loops. We focused the analysis on highly recurrent words of loops (observed more than 30 times). Our study reveals that 73% of loop-lengths are covered by only 3310 highly recurrent structural words out of 28274 observed words). These structural words have low structural variability (mean RMSd of 0.85 Å). As expected, half of these motifs display a flanking-region preference but interestingly, two thirds are shared by short (less than 12 residues) and long loops. Moreover, half of recurrent motifs exhibit a significant level of amino-acid conservation with at least four significant positions and 87% of long loops contain at least one such word. We complement our analysis with the detection of statistically over-represented patterns of structural letters as in conventional DNA sequence analysis. About 30% (930) of structural words are over-represented, and cover about 40% of loop lengths. Interestingly, these words exhibit lower structural variability and higher sequential specificity, suggesting structural or functional constraints. Conclusions: We developed a method to systematically decompose and study protein loops using recurrent structural motifs. This method is based on the structural alphabet HMM-SA and not on structural alignment and geometrical parameters. We extracted meaningful structural motifs that are found in both short and long loops. To our knowledge, it is the first time that pattern mining helps to increase the signal-to-noise ratio in protein loops. This finding helps to better describe protein loops and might permit to decrease the complexity of long-loop analysis. Detailed results are available at
<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1186/1471-2105-11-75">doi:10.1186/1471-2105-11-75</a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pubmed/20132552">pmid:20132552</a> <a target="_blank" rel="external noopener" href="https://pubmed.ncbi.nlm.nih.gov/PMC2833150/">pmcid:PMC2833150</a> <a target="_blank" rel="external noopener" href="https://fatcat.wiki/release/xwgkzwnimvecxbgwfbq36o5dsa">fatcat:xwgkzwnimvecxbgwfbq36o5dsa</a> </span>
<a target="_blank" rel="noopener" href="https://web.archive.org/web/20190311070105/https://core.ac.uk/download/pdf/47104448.pdf" title="fulltext PDF download" data-goatcounter-click="serp-fulltext" data-goatcounter-title="serp-fulltext"> <button class="ui simple right pointing dropdown compact black labeled icon button serp-button"> <i class="icon ia-icon"></i> Web Archive [PDF] <div class="menu fulltext-thumbnail"> <img src="https://blobs.fatcat.wiki/thumbnail/pdf/39/fc/39fc5819d028f5e3393813a91d069d70f5e5eb51.180px.jpg" alt="fulltext thumbnail" loading="lazy"> </div> </button> </a> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1186/1471-2105-11-75"> <button class="ui left aligned compact blue labeled icon button serp-button"> <i class="unlock alternate icon" style="background-color: #fb971f;"></i> springer.com </button> </a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2833150" title="pubmed link"> <button class="ui compact blue labeled icon button serp-button"> <i class="file alternate outline icon"></i> pubmed.gov </button> </a>

Structural deformation upon protein-protein interaction: A structural alphabet approach

Juliette Martin, Leslie Regad, Hélène Lecornet, Anne-Claude Camproux
<span title="">2008</span> <i title="Springer Nature"> <a target="_blank" rel="noopener" href="https://fatcat.wiki/container/m36qvjwuvnegpgzopqbhvg7k3e" style="color: black;">BMC Structural Biology</a> </i> &nbsp;
<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1186/1472-6807-8-12">doi:10.1186/1472-6807-8-12</a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pubmed/18307769">pmid:18307769</a> <a target="_blank" rel="external noopener" href="https://pubmed.ncbi.nlm.nih.gov/PMC2315654/">pmcid:PMC2315654</a> <a target="_blank" rel="external noopener" href="https://fatcat.wiki/release/7njveh23pzdltiyn36xadjlysi">fatcat:7njveh23pzdltiyn36xadjlysi</a> </span>
<a target="_blank" rel="noopener" href="https://web.archive.org/web/20201108020431/https://hal.inrae.fr/hal-02662156/document" title="fulltext PDF download" data-goatcounter-click="serp-fulltext" data-goatcounter-title="serp-fulltext"> <button class="ui simple right pointing dropdown compact black labeled icon button serp-button"> <i class="icon ia-icon"></i> Web Archive [PDF] <div class="menu fulltext-thumbnail"> <img src="https://blobs.fatcat.wiki/thumbnail/pdf/76/68/76682a840d87a3b8d7155a50c1ea1a2ae2740745.180px.jpg" alt="fulltext thumbnail" loading="lazy"> </div> </button> </a> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1186/1472-6807-8-12"> <button class="ui left aligned compact blue labeled icon button serp-button"> <i class="unlock alternate icon" style="background-color: #fb971f;"></i> springer.com </button> </a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2315654" title="pubmed link"> <button class="ui compact blue labeled icon button serp-button"> <i class="file alternate outline icon"></i> pubmed.gov </button> </a>

Application of HMM to the Study of Three-Dimensional Protein Structure [chapter]

Christelle Reyns, Leslie Regad, Stphanie Prot, Grgory Nuel, Anne-Claude Camproux
<span title="2011-04-19">2011</span> <i title="InTech"> Hidden Markov Models, Theory and Applications </i> &nbsp;
These results are detailed in Camproux et al. (1999b; . Actually, SLs associated with close shapes have been distinguished by different logical rules.  ...  Protein structures are described using the distances between C α , see Figure 1a , as series of overlapping fragments of four-residue length (Camproux et al., 1999a) . Let C α 1 , C α 2 ,...  ...  How to reference In order to correctly reference this scholarly work, feel free to copy and paste the following: Christelle Reynès, Leslie Regad, Stéphanie Pérot, Grégory Nuel and Anne-Claude Camproux  ... 
<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.5772/14503">doi:10.5772/14503</a> <a target="_blank" rel="external noopener" href="https://fatcat.wiki/release/alu7bgwfqfgrpntaoycf5o6myy">fatcat:alu7bgwfqfgrpntaoycf5o6myy</a> </span>
<a target="_blank" rel="noopener" href="https://web.archive.org/web/20190503190614/https://cdn.intechopen.com/pdfs/15367.pdf" title="fulltext PDF download" data-goatcounter-click="serp-fulltext" data-goatcounter-title="serp-fulltext"> <button class="ui simple right pointing dropdown compact black labeled icon button serp-button"> <i class="icon ia-icon"></i> Web Archive [PDF] <div class="menu fulltext-thumbnail"> <img src="https://blobs.fatcat.wiki/thumbnail/pdf/6b/e0/6be066bce2e88aff011bb66d62dfdccfa7cb6003.180px.jpg" alt="fulltext thumbnail" loading="lazy"> </div> </button> </a> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.5772/14503"> <button class="ui left aligned compact blue labeled icon button serp-button"> <i class="external alternate icon"></i> Publisher / doi.org </button> </a>

Cavity Versus Ligand Shape Descriptors: Application to Urokinase Binding Pockets

Natacha Cerisier, Leslie Regad, Dhoha Triki, Anne-Claude Camproux, Michel Petitjean
<span title="">2017</span> <i title="Mary Ann Liebert Inc"> <a target="_blank" rel="noopener" href="https://fatcat.wiki/container/id6xbd2o6fhy7pts2djgwhtmvy" style="color: black;">Journal of Computational Biology</a> </i> &nbsp;
We analyzed 78 binding pockets of the human urokinase plasminogen activator (uPA) catalytic domain extracted from a data set of crystallized uPA-ligand complexes. These binding pockets were computed with an original geometric method that does NOT involve any arbitrary parameter, such as cutoff distances, angles, and so on. We measured the deviation from convexity of each pocket shape with the pocket convexity index (PCI). We defined a new pocket descriptor called distributional sphericity
more &raquo; ... cient (DISC), which indicates to which extent the protein atoms of a given pocket lie on the surface of a sphere. The DISC values were computed with the freeware PCI. The pocket descriptors and their high correspondences with ligand descriptors are crucial for polypharmacology prediction. We found that the protein heavy atoms lining the urokinases binding pockets are either located on the surface of their convex hull or lie close to this surface. We also found that the radii of the urokinases binding pockets and the radii of their ligands are highly correlated (r 5 0.9).
<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1089/cmb.2017.0061">doi:10.1089/cmb.2017.0061</a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pubmed/28570103">pmid:28570103</a> <a target="_blank" rel="external noopener" href="https://pubmed.ncbi.nlm.nih.gov/PMC5684670/">pmcid:PMC5684670</a> <a target="_blank" rel="external noopener" href="https://fatcat.wiki/release/qjddh7bww5gcna45dpw3jfx2jq">fatcat:qjddh7bww5gcna45dpw3jfx2jq</a> </span>
<a target="_blank" rel="noopener" href="https://web.archive.org/web/20190303121316/http://pdfs.semanticscholar.org/c933/c46ae366d925b885333833d1186785c7d7d7.pdf" title="fulltext PDF download" data-goatcounter-click="serp-fulltext" data-goatcounter-title="serp-fulltext"> <button class="ui simple right pointing dropdown compact black labeled icon button serp-button"> <i class="icon ia-icon"></i> Web Archive [PDF] <div class="menu fulltext-thumbnail"> <img src="https://blobs.fatcat.wiki/thumbnail/pdf/c9/33/c933c46ae366d925b885333833d1186785c7d7d7.180px.jpg" alt="fulltext thumbnail" loading="lazy"> </div> </button> </a> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1089/cmb.2017.0061"> <button class="ui left aligned compact blue labeled icon button serp-button"> <i class="external alternate icon"></i> Publisher / doi.org </button> </a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5684670" title="pubmed link"> <button class="ui compact blue labeled icon button serp-button"> <i class="file alternate outline icon"></i> pubmed.gov </button> </a>

In silicolocal structure approach: A case study on Outer Membrane Proteins

Juliette Martin, Alexandre G. de Brevern, Anne-Claude Camproux
<span title="">2008</span> <i title="Wiley"> <a target="_blank" rel="noopener" href="https://fatcat.wiki/container/fkowqlvuffe5lnyfwblj3fcp7i" style="color: black;">Proteins: Structure, Function, and Bioinformatics</a> </i> &nbsp;
Originality of SA20-OMP We used the approach developed by Camproux et al [31, 34] that defined a generic alphabet, SA27.  ...  This analysis is based on the likelihood of the structures under three different alphabets: SA20-OMP, SA20-GB and the alphabet previously introduced by Camproux et al [34] .  ... 
<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1002/prot.21659">doi:10.1002/prot.21659</a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pubmed/17932925">pmid:17932925</a> <a target="_blank" rel="external noopener" href="https://fatcat.wiki/release/pljiqjxbozd67bchlcwjk3qhfi">fatcat:pljiqjxbozd67bchlcwjk3qhfi</a> </span>
<a target="_blank" rel="noopener" href="https://web.archive.org/web/20190218180830/https://core.ac.uk/download/pdf/47119075.pdf" title="fulltext PDF download" data-goatcounter-click="serp-fulltext" data-goatcounter-title="serp-fulltext"> <button class="ui simple right pointing dropdown compact black labeled icon button serp-button"> <i class="icon ia-icon"></i> Web Archive [PDF] <div class="menu fulltext-thumbnail"> <img src="https://blobs.fatcat.wiki/thumbnail/pdf/06/60/06605b6257f3106bd9c03990ef5da5c7a645964c.180px.jpg" alt="fulltext thumbnail" loading="lazy"> </div> </button> </a> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1002/prot.21659"> <button class="ui left aligned compact blue labeled icon button serp-button"> <i class="external alternate icon"></i> wiley.com </button> </a>

Dissecting protein loops with a statistical scalpel suggests a functional implication of some structural motifs

Leslie Regad, Juliette Martin, Anne-Claude Camproux
<span title="">2011</span> <i title="Springer Nature"> <a target="_blank" rel="noopener" href="https://fatcat.wiki/container/n5zrklrhlzhtdorf4rk4rmeo3i" style="color: black;">BMC Bioinformatics</a> </i> &nbsp;
One of the strategies for protein function annotation is to search particular structural motifs that are known to be shared by proteins with a given function. Results: Here, we present a systematic extraction of structural motifs of seven residues from protein loops and we explore their correspondence with functional sites. Our approach is based on the structural alphabet HMM-SA (Hidden Markov Model -Structural Alphabet), which allows simplification of protein structures into uni-dimensional
more &raquo; ... uences, and advanced pattern statistics adapted to short sequences. Structural motifs of interest are selected by looking for structural motifs significantly over-represented in SCOP superfamilies in protein loops. We discovered two types of structural motifs significantly over-represented in SCOP superfamilies: (i) ubiquitous motifs, shared by several superfamilies and (ii) superfamily-specific motifs, over-represented in few superfamilies. A comparison of ubiquitous words with known small structural motifs shows that they contain well-described motifs as turn, niche or nest motifs. A comparison between superfamily-specific motifs and biological annotations of Swiss-Prot reveals that some of them actually correspond to functional sites involved in the binding sites of small ligands, such as ATP/GTP, NAD(P) and SAH/SAM. Conclusions: Our findings show that statistical over-representation in SCOP superfamilies is linked to functional features. The detection of over-represented motifs within structures simplified by HMM-SA is therefore a promising approach for prediction of functional sites and annotation of uncharacterized proteins.
<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1186/1471-2105-12-247">doi:10.1186/1471-2105-12-247</a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pubmed/21689388">pmid:21689388</a> <a target="_blank" rel="external noopener" href="https://pubmed.ncbi.nlm.nih.gov/PMC3158783/">pmcid:PMC3158783</a> <a target="_blank" rel="external noopener" href="https://fatcat.wiki/release/v2de52nu3jcbxdzjt5jyhpnghe">fatcat:v2de52nu3jcbxdzjt5jyhpnghe</a> </span>
<a target="_blank" rel="noopener" href="https://web.archive.org/web/20190417015813/https://core.ac.uk/download/pdf/47105784.pdf" title="fulltext PDF download" data-goatcounter-click="serp-fulltext" data-goatcounter-title="serp-fulltext"> <button class="ui simple right pointing dropdown compact black labeled icon button serp-button"> <i class="icon ia-icon"></i> Web Archive [PDF] <div class="menu fulltext-thumbnail"> <img src="https://blobs.fatcat.wiki/thumbnail/pdf/d6/b0/d6b06ef1c7649abf41391548d139d469cda114b4.180px.jpg" alt="fulltext thumbnail" loading="lazy"> </div> </button> </a> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1186/1471-2105-12-247"> <button class="ui left aligned compact blue labeled icon button serp-button"> <i class="unlock alternate icon" style="background-color: #fb971f;"></i> springer.com </button> </a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3158783" title="pubmed link"> <button class="ui compact blue labeled icon button serp-button"> <i class="file alternate outline icon"></i> pubmed.gov </button> </a>

A non-parametric method to compute protein-protein and protein-ligands interfaces. Application to HIV-2 protease-inhibitors complexes [article]

Pierre Laville, Juliette Martin, Guillaume Launay, Leslie Regad, Anne-Claude Camproux, Sjoerd de Vries, Michel Petitjean
<span title="2018-12-18">2018</span> <i title="Cold Spring Harbor Laboratory"> bioRxiv </i> &nbsp; <span class="release-stage" >pre-print</span>
Motivation: The accurate description of interfaces is needed to identify which residues interact with another molecule or macromolecule. In addition, a data structure is required to compare interfaces within or between families of protein-protein or protein-ligands complexes. In order to avoid many unwanted comparisons, we looked for a parameter free computation of interfaces. This need appeared at the occasion of bioinformatics studies by our research team focusing on HIV-2 protease (PR2)
more &raquo; ... tance to its inhibitors. Results: We designed the PPIC software (Protein Protein Interface Computation). It offers three methods of computation of interfaces: (1) our original parameter free method, (2) the Voronoi tessellation approach, and (3) the cutoff distance method. For the latter, we suggest on the basis of 1050 dimers protein-protein interfaces that the optimal cutoff distance is 3.7 Å, or 3.6 Å for a set of 18 PR2-ligand interfaces. We found at most 17 contact residues with PR2 ligands. Availability: Free binaries and documentation are available through a software repository located at http://petitjeanmichel.free.fr/itoweb.petitjean.freeware.html
<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1101/498923">doi:10.1101/498923</a> <a target="_blank" rel="external noopener" href="https://fatcat.wiki/release/sudhxhzxezfj7l3dhi3dpnm6me">fatcat:sudhxhzxezfj7l3dhi3dpnm6me</a> </span>
<a target="_blank" rel="noopener" href="https://web.archive.org/web/20190502093536/https://www.biorxiv.org/content/biorxiv/early/2018/12/18/498923.full.pdf" title="fulltext PDF download" data-goatcounter-click="serp-fulltext" data-goatcounter-title="serp-fulltext"> <button class="ui simple right pointing dropdown compact black labeled icon button serp-button"> <i class="icon ia-icon"></i> Web Archive [PDF] <div class="menu fulltext-thumbnail"> <img src="https://blobs.fatcat.wiki/thumbnail/pdf/24/a6/24a676b6e9f0e4907544375d2964880ebeb7f31c.180px.jpg" alt="fulltext thumbnail" loading="lazy"> </div> </button> </a> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1101/498923"> <button class="ui left aligned compact blue labeled icon button serp-button"> <i class="external alternate icon"></i> biorxiv.org </button> </a>

Exploring the Structural Rearrangements of the Human Insulin-Degrading Enzyme through Molecular Dynamics Simulations

Mariem Ghoula, Nathalie Janel, Anne-Claude Camproux, Gautier Moroy
<span title="2022-02-03">2022</span> <i title="MDPI AG"> <a target="_blank" rel="noopener" href="https://fatcat.wiki/container/3loumxx7kzamnlu4h6x3xoz6ay" style="color: black;">International Journal of Molecular Sciences</a> </i> &nbsp;
Insulin-degrading enzyme (IDE) is a ubiquitously expressed metallopeptidase that degrades insulin and a large panel of amyloidogenic peptides. IDE is thought to be a potential therapeutic target for type-2 diabetes and neurodegenerative diseases, such as Alzheimer's disease. IDE catalytic chamber, known as a crypt, is formed, so that peptides can be enclosed and degraded. However, the molecular mechanism of the IDE function and peptide recognition, as well as its conformation changes, remains
more &raquo; ... usive. Our study elucidates IDE structural changes and explains how IDE conformational dynamics is important to modulate the catalytic cycle of IDE. In this aim, a free-substrate IDE crystallographic structure (PDB ID: 2JG4) was used to model a complete structure of IDE. IDE stability and flexibility were studied through molecular dynamics (MD) simulations to witness IDE conformational dynamics switching from a closed to an open state. The description of IDE structural changes was achieved by analysis of the cavity and its expansion over time. Moreover, the quasi-harmonic analysis of the hinge connecting IDE domains and the angles formed over the simulations gave more insights into IDE shifts. Overall, our results could guide toward the use of different approaches to study IDE with different substrates and inhibitors, while taking into account the conformational states resolved in our study.
<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.3390/ijms23031746">doi:10.3390/ijms23031746</a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pubmed/35163673">pmid:35163673</a> <a target="_blank" rel="external noopener" href="https://pubmed.ncbi.nlm.nih.gov/PMC8836115/">pmcid:PMC8836115</a> <a target="_blank" rel="external noopener" href="https://fatcat.wiki/release/c3u24oqvhncbzndnw4qdvlzxry">fatcat:c3u24oqvhncbzndnw4qdvlzxry</a> </span>
<a target="_blank" rel="noopener" href="https://web.archive.org/web/20220208230559/https://mdpi-res.com/d_attachment/ijms/ijms-23-01746/article_deploy/ijms-23-01746.pdf" title="fulltext PDF download" data-goatcounter-click="serp-fulltext" data-goatcounter-title="serp-fulltext"> <button class="ui simple right pointing dropdown compact black labeled icon button serp-button"> <i class="icon ia-icon"></i> Web Archive [PDF] <div class="menu fulltext-thumbnail"> <img src="https://blobs.fatcat.wiki/thumbnail/pdf/87/5d/875de5754527372267de72d64248607fdb4fd944.180px.jpg" alt="fulltext thumbnail" loading="lazy"> </div> </button> </a> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.3390/ijms23031746"> <button class="ui left aligned compact blue labeled icon button serp-button"> <i class="unlock alternate icon" style="background-color: #fb971f;"></i> mdpi.com </button> </a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8836115" title="pubmed link"> <button class="ui compact blue labeled icon button serp-button"> <i class="file alternate outline icon"></i> pubmed.gov </button> </a>

Characterization of HIV-2 Protease Structure by Studying Its Asymmetry at the Different Levels of Protein Description

Guillaume Ollitrault, Sandrine Fartek, Diane Descamps, Anne-Claude Camproux, Benoît Visseaux, Leslie Regad
<span title="2018-11-16">2018</span> <i title="MDPI AG"> <a target="_blank" rel="noopener" href="https://fatcat.wiki/container/nzoj5rayr5hutlurimhzyjlory" style="color: black;">Symmetry</a> </i> &nbsp;
HIV-2 protease (PR2) is a homodimer, which is an important target in the treatment of the HIV-2 infection. In this study, we developed an in silico protocol to analyze and characterize the asymmetry of the unbound PR2 structure using three levels of protein description by comparing the conformation, accessibility, and flexibility of each residue in the two PR2 chains. Our results showed that 65% of PR2 residues have at least one of the three studied asymmetries (structural, accessibility, or
more &raquo; ... xibility) with 10 positions presenting the three asymmetries in the same time. In addition, we noted that structural and flexibility asymmetries are linked indicating that the structural asymmetry of some positions result from their large flexibility. By comparing the structural asymmetry of the crystallographic and energetically minimized structures of the unbound PR2, we confirmed that the structural asymmetry of unbound PR2 is an intrinsic property of this protein with an important role for the PR2 deformation upon ligand binding. This analysis also allowed locating asymmetries corresponding to crystallization artefacts. This study provides insight that will help to better understand the structural deformations of PR2 and to identify key positions for ligand binding.
<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.3390/sym10110644">doi:10.3390/sym10110644</a> <a target="_blank" rel="external noopener" href="https://fatcat.wiki/release/gjttaststbf57ctmoiapzsgu2a">fatcat:gjttaststbf57ctmoiapzsgu2a</a> </span>
<a target="_blank" rel="noopener" href="https://web.archive.org/web/20190502100338/https://res.mdpi.com/symmetry/symmetry-10-00644/article_deploy/symmetry-10-00644.pdf?filename=&amp;attachment=1" title="fulltext PDF download" data-goatcounter-click="serp-fulltext" data-goatcounter-title="serp-fulltext"> <button class="ui simple right pointing dropdown compact black labeled icon button serp-button"> <i class="icon ia-icon"></i> Web Archive [PDF] <div class="menu fulltext-thumbnail"> <img src="https://blobs.fatcat.wiki/thumbnail/pdf/58/06/5806c41ca0d6db7ddc47e0ce70836cdbd53de3cd.180px.jpg" alt="fulltext thumbnail" loading="lazy"> </div> </button> </a> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.3390/sym10110644"> <button class="ui left aligned compact blue labeled icon button serp-button"> <i class="unlock alternate icon" style="background-color: #fb971f;"></i> mdpi.com </button> </a>

SA-Mot: a web server for the identification of motifs of interest extracted from protein loops

Leslie Regad, Adrien Saladin, Julien Maupetit, Colette Geneix, Anne-Claude Camproux
<span title="2011-06-10">2011</span> <i title="Oxford University Press (OUP)"> <a target="_blank" rel="noopener" href="https://fatcat.wiki/container/hfp6p6inqbdexbsu4r7usndpte" style="color: black;">Nucleic Acids Research</a> </i> &nbsp;
The detection of functional motifs is an important step for the determination of protein functions. We present here a new web server SA-Mot (Structural Alphabet Motif) for the extraction and location of structural motifs of interest from protein loops. Contrary to other methods, SA-Mot does not focus only on functional motifs, but it extracts recurrent and conserved structural motifs involved in structural redundancy of loops. SA-Mot uses the structural word notion to extract all structural
more &raquo; ... fs from uni-dimensional sequences corresponding to loop structures. Then, SA-Mot provides a description of these structural motifs using statistics computed in the loop data set and in SCOP superfamily, sequence and structural parameters. SA-Mot results correspond to an interactive table listing all structural motifs extracted from a target structure and their associated descriptors. Using this information, the users can easily locate loop regions that are important for the protein folding and function. The SA-Mot web server is available at
<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1093/nar/gkr410">doi:10.1093/nar/gkr410</a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pubmed/21665924">pmid:21665924</a> <a target="_blank" rel="external noopener" href="https://pubmed.ncbi.nlm.nih.gov/PMC3125790/">pmcid:PMC3125790</a> <a target="_blank" rel="external noopener" href="https://fatcat.wiki/release/hmiaavkhcrb5ll4cs2s7mrwkyi">fatcat:hmiaavkhcrb5ll4cs2s7mrwkyi</a> </span>
<a target="_blank" rel="noopener" href="https://web.archive.org/web/20190308082542/http://pdfs.semanticscholar.org/efc8/f16dc8a91b16e9efd822b77a4cc5570252d2.pdf" title="fulltext PDF download" data-goatcounter-click="serp-fulltext" data-goatcounter-title="serp-fulltext"> <button class="ui simple right pointing dropdown compact black labeled icon button serp-button"> <i class="icon ia-icon"></i> Web Archive [PDF] <div class="menu fulltext-thumbnail"> <img src="https://blobs.fatcat.wiki/thumbnail/pdf/ef/c8/efc8f16dc8a91b16e9efd822b77a4cc5570252d2.180px.jpg" alt="fulltext thumbnail" loading="lazy"> </div> </button> </a> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1093/nar/gkr410"> <button class="ui left aligned compact blue labeled icon button serp-button"> <i class="unlock alternate icon" style="background-color: #fb971f;"></i> oup.com </button> </a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3125790" title="pubmed link"> <button class="ui compact blue labeled icon button serp-button"> <i class="file alternate outline icon"></i> pubmed.gov </button> </a>

SAFlex: A structural alphabet extension to integrate protein structural flexibility and missing data information

Ikram Allam, Delphine Flatters, Géraldine Caumes, Leslie Regad, Vincent Delos, Gregory Nuel, Anne-Claude Camproux, Manuela Helmer-Citterich
<span title="2018-07-05">2018</span> <i title="Public Library of Science (PLoS)"> <a target="_blank" rel="noopener" href="https://fatcat.wiki/container/s3gm7274mfe6fcs7e3jterqlri" style="color: black;">PLoS ONE</a> </i> &nbsp;
(TEX) Supervision: Gregory Nuel, Anne-Claude Camproux. Validation: Ikram Allam, Delphine Flatters, Gregory Nuel, Anne-Claude Camproux. Visualization: Ikram Allam, Gregory Nuel.  ...  Writing -original draft: Ikram Allam, Gregory Nuel, Anne-Claude Camproux.  ... 
<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1371/journal.pone.0198854">doi:10.1371/journal.pone.0198854</a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pubmed/29975698">pmid:29975698</a> <a target="_blank" rel="external noopener" href="https://pubmed.ncbi.nlm.nih.gov/PMC6033379/">pmcid:PMC6033379</a> <a target="_blank" rel="external noopener" href="https://fatcat.wiki/release/5lnvmvc3fvbgfcgczqfj4z5lni">fatcat:5lnvmvc3fvbgfcgczqfj4z5lni</a> </span>
<a target="_blank" rel="noopener" href="https://web.archive.org/web/20190226071645/http://pdfs.semanticscholar.org/6e2d/95fad4d36fe7d60ce88e2ccfe4bbcf6f3f97.pdf" title="fulltext PDF download" data-goatcounter-click="serp-fulltext" data-goatcounter-title="serp-fulltext"> <button class="ui simple right pointing dropdown compact black labeled icon button serp-button"> <i class="icon ia-icon"></i> Web Archive [PDF] <div class="menu fulltext-thumbnail"> <img src="https://blobs.fatcat.wiki/thumbnail/pdf/6e/2d/6e2d95fad4d36fe7d60ce88e2ccfe4bbcf6f3f97.180px.jpg" alt="fulltext thumbnail" loading="lazy"> </div> </button> </a> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1371/journal.pone.0198854"> <button class="ui left aligned compact blue labeled icon button serp-button"> <i class="unlock alternate icon" style="background-color: #fb971f;"></i> plos.org </button> </a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6033379" title="pubmed link"> <button class="ui compact blue labeled icon button serp-button"> <i class="file alternate outline icon"></i> pubmed.gov </button> </a>

Insights into an Original Pocket-Ligand Pair Classification: A Promising Tool for Ligand Profile Prediction

Stéphanie Pérot, Leslie Regad, Christelle Reynès, Olivier Spérandio, Maria A. Miteva, Bruno O. Villoutreix, Anne-Claude Camproux, Lukasz Kurgan
<span title="2013-06-20">2013</span> <i title="Public Library of Science (PLoS)"> <a target="_blank" rel="noopener" href="https://fatcat.wiki/container/s3gm7274mfe6fcs7e3jterqlri" style="color: black;">PLoS ONE</a> </i> &nbsp;
Pockets are today at the cornerstones of modern drug discovery projects and at the crossroad of several research fields, from structural biology to mathematical modeling. Being able to predict if a small molecule could bind to one or more protein targets or if a protein could bind to some given ligands is very useful for drug discovery endeavors, anticipation of binding to off-and anti-targets. To date, several studies explore such questions from chemogenomic approach to reverse docking
more &raquo; ... Most of these studies have been performed either from the viewpoint of ligands or targets. However it seems valuable to use information from both ligands and target binding pockets. Hence, we present a multivariate approach relating ligand properties with protein pocket properties from the analysis of known ligand-protein interactions. We explored and optimized the pocket-ligand pair space by combining pocket and ligand descriptors using Principal Component Analysis and developed a classification engine on this paired space, revealing five main clusters of pocketligand pairs sharing specific and similar structural or physico-chemical properties. These pocket-ligand pair clusters highlight correspondences between pocket and ligand topological and physico-chemical properties and capture relevant information with respect to protein-ligand interactions. Based on these pocket-ligand correspondences, a protocol of prediction of clusters sharing similarity in terms of recognition characteristics is developed for a given pocket-ligand complex and gives high performances. It is then extended to cluster prediction for a given pocket in order to acquire knowledge about its expected ligand profile or to cluster prediction for a given ligand in order to acquire knowledge about its expected pocket profile. This prediction approach shows promising results and could contribute to predict some ligand properties critical for binding to a given pocket, and conversely, some key pocket properties for ligand binding.
<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1371/journal.pone.0063730">doi:10.1371/journal.pone.0063730</a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pubmed/23840299">pmid:23840299</a> <a target="_blank" rel="external noopener" href="https://pubmed.ncbi.nlm.nih.gov/PMC3688729/">pmcid:PMC3688729</a> <a target="_blank" rel="external noopener" href="https://fatcat.wiki/release/72uftyvduzfm5a3crjr7vaxaae">fatcat:72uftyvduzfm5a3crjr7vaxaae</a> </span>
<a target="_blank" rel="noopener" href="https://web.archive.org/web/20171007031552/http://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0063730&amp;type=printable" title="fulltext PDF download" data-goatcounter-click="serp-fulltext" data-goatcounter-title="serp-fulltext"> <button class="ui simple right pointing dropdown compact black labeled icon button serp-button"> <i class="icon ia-icon"></i> Web Archive [PDF] <div class="menu fulltext-thumbnail"> <img src="https://blobs.fatcat.wiki/thumbnail/pdf/e4/ee/e4ee90e25b33e38123b10e2af47d7838ea666174.180px.jpg" alt="fulltext thumbnail" loading="lazy"> </div> </button> </a> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1371/journal.pone.0063730"> <button class="ui left aligned compact blue labeled icon button serp-button"> <i class="unlock alternate icon" style="background-color: #fb971f;"></i> plos.org </button> </a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3688729" title="pubmed link"> <button class="ui compact blue labeled icon button serp-button"> <i class="file alternate outline icon"></i> pubmed.gov </button> </a>

Designing Focused Chemical Libraries Enriched in Protein-Protein Interaction Inhibitors using Machine-Learning Methods

Christelle Reynès, Hélène Host, Anne-Claude Camproux, Guillaume Laconde, Florence Leroux, Anne Mazars, Benoit Deprez, Robin Fahraeus, Bruno O. Villoutreix, Olivier Sperandio, Philip E. Bourne
<span title="2010-03-05">2010</span> <i title="Public Library of Science (PLoS)"> <a target="_blank" rel="noopener" href="https://fatcat.wiki/container/ch57atmlprauhhbqdf7x4ytejm" style="color: black;">PLoS Computational Biology</a> </i> &nbsp;
Protein-protein interactions (PPIs) may represent one of the next major classes of therapeutic targets. So far, only a minute fraction of the estimated 650,000 PPIs that comprise the human interactome are known with a tiny number of complexes being drugged. Such intricate biological systems cannot be cost-efficiently tackled using conventional high-throughput screening methods. Rather, time has come for designing new strategies that will maximize the chance for hit identification through a
more &raquo; ... nalization of the PPI inhibitor chemical space and the design of PPI-focused compound libraries (global or target-specific). Here, we train machine-learning-based models, mainly decision trees, using a dataset of known PPI inhibitors and of regular drugs in order to determine a global physico-chemical profile for putative PPI inhibitors. This statistical analysis unravels two important molecular descriptors for PPI inhibitors characterizing specific molecular shapes and the presence of a privileged number of aromatic bonds. The best model has been transposed into a computer program, PPI-HitProfiler, that can output from any drug-like compound collection a focused chemical library enriched in putative PPI inhibitors. Our PPI inhibitor profiler is challenged on the experimental screening results of 11 different PPIs among which the p53/MDM2 interaction screened within our own CDithem platform, that in addition to the validation of our concept led to the identification of 4 novel p53/MDM2 inhibitors. Collectively, our tool shows a robust behavior on the 11 experimental datasets by correctly profiling 70% of the experimentally identified hits while removing 52% of the inactive compounds from the initial compound collections. We strongly believe that this new tool can be used as a global PPI inhibitor profiler prior to screening assays to reduce the size of the compound collections to be experimentally screened while keeping most of the true PPI inhibitors. PPI-HitProfiler is freely available on request from our CDithem platform website, www.CDithem.com.
<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1371/journal.pcbi.1000695">doi:10.1371/journal.pcbi.1000695</a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pubmed/20221258">pmid:20221258</a> <a target="_blank" rel="external noopener" href="https://pubmed.ncbi.nlm.nih.gov/PMC2832677/">pmcid:PMC2832677</a> <a target="_blank" rel="external noopener" href="https://fatcat.wiki/release/dwi7e2ndmfcublzqxiyfeogq6e">fatcat:dwi7e2ndmfcublzqxiyfeogq6e</a> </span>
<a target="_blank" rel="noopener" href="https://web.archive.org/web/20171015131553/http://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1000695&amp;type=printable" title="fulltext PDF download" data-goatcounter-click="serp-fulltext" data-goatcounter-title="serp-fulltext"> <button class="ui simple right pointing dropdown compact black labeled icon button serp-button"> <i class="icon ia-icon"></i> Web Archive [PDF] <div class="menu fulltext-thumbnail"> <img src="https://blobs.fatcat.wiki/thumbnail/pdf/5a/ea/5aea8f01f530b4d085874c142b8e7f9737d69e3b.180px.jpg" alt="fulltext thumbnail" loading="lazy"> </div> </button> </a> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1371/journal.pcbi.1000695"> <button class="ui left aligned compact blue labeled icon button serp-button"> <i class="unlock alternate icon" style="background-color: #fb971f;"></i> plos.org </button> </a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2832677" title="pubmed link"> <button class="ui compact blue labeled icon button serp-button"> <i class="file alternate outline icon"></i> pubmed.gov </button> </a>

PockDrug-Server: a new web server for predicting pocket druggability on holo and apo proteins

Hiba Abi Hussein, Alexandre Borrel, Colette Geneix, Michel Petitjean, Leslie Regad, Anne-Claude Camproux
<span title="2015-05-08">2015</span> <i title="Oxford University Press (OUP)"> <a target="_blank" rel="noopener" href="https://fatcat.wiki/container/hfp6p6inqbdexbsu4r7usndpte" style="color: black;">Nucleic Acids Research</a> </i> &nbsp;
Predicting protein pocket's ability to bind drug-like molecules with high affinity, i.e. druggability, is of major interest in the target identification phase of drug discovery. Therefore, pocket druggability investigations represent a key step of compound clinical progression projects. Currently computational druggability prediction models are attached to one unique pocket estimation method despite pocket estimation uncertainties. In this paper, we propose 'PockDrug-Server' to predict pocket
more &raquo; ... uggability, efficient on both (i) estimated pockets guided by the ligand proximity (extracted by proximity to a ligand from a holo protein structure) and (ii) estimated pockets based solely on protein structure information (based on amino atoms that form the surface of potential binding cavities). PockDrug-Server provides consistent druggability results using different pocket estimation methods. It is robust with respect to pocket boundary and estimation uncertainties, thus efficient using apo pockets that are challenging to estimate. It clearly distinguishes druggable from less druggable pockets using different estimation methods and outperformed recent druggability models for apo pockets. It can be carried out from one or a set of apo/holo proteins using different pocket estimation methods proposed by our web server or from any pocket previously estimated by the user. PockDrug-Server is publicly available at: http://pockdrug.rpbs.univ-paris-diderot.fr.
<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1093/nar/gkv462">doi:10.1093/nar/gkv462</a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pubmed/25956651">pmid:25956651</a> <a target="_blank" rel="external noopener" href="https://pubmed.ncbi.nlm.nih.gov/PMC4489252/">pmcid:PMC4489252</a> <a target="_blank" rel="external noopener" href="https://fatcat.wiki/release/36ovg3id5jdptafmu4eshjmbay">fatcat:36ovg3id5jdptafmu4eshjmbay</a> </span>
<a target="_blank" rel="noopener" href="https://web.archive.org/web/20190223143227/http://pdfs.semanticscholar.org/510a/277c36a0c734f6f8641269a325b36011d10d.pdf" title="fulltext PDF download" data-goatcounter-click="serp-fulltext" data-goatcounter-title="serp-fulltext"> <button class="ui simple right pointing dropdown compact black labeled icon button serp-button"> <i class="icon ia-icon"></i> Web Archive [PDF] <div class="menu fulltext-thumbnail"> <img src="https://blobs.fatcat.wiki/thumbnail/pdf/51/0a/510a277c36a0c734f6f8641269a325b36011d10d.180px.jpg" alt="fulltext thumbnail" loading="lazy"> </div> </button> </a> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1093/nar/gkv462"> <button class="ui left aligned compact blue labeled icon button serp-button"> <i class="unlock alternate icon" style="background-color: #fb971f;"></i> oup.com </button> </a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4489252" title="pubmed link"> <button class="ui compact blue labeled icon button serp-button"> <i class="file alternate outline icon"></i> pubmed.gov </button> </a>
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