{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T09:05:59Z","timestamp":1762074359404,"version":"build-2065373602"},"reference-count":40,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,11,7]],"date-time":"2022-11-07T00:00:00Z","timestamp":1667779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001665","name":"\u201cInitiative d\u2019Excellence\u201d program from the French State","doi-asserted-by":"publisher","award":["ANR-11-LABX-0011","ANR-11-EQPX-0008","13016382"],"award-info":[{"award-number":["ANR-11-LABX-0011","ANR-11-EQPX-0008","13016382"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Sesame Ile-de-France","award":["ANR-11-LABX-0011","ANR-11-EQPX-0008","13016382"],"award-info":[{"award-number":["ANR-11-LABX-0011","ANR-11-EQPX-0008","13016382"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Algorithms"],"abstract":"<jats:p>(1) Background: We developed an algorithm to perform interactive molecular simulations (IMS) of protein alignment in membranes, allowing on-the-fly monitoring and manipulation of such molecular systems at various scales. (2) Methods: UnityMol, an advanced molecular visualization software; MDDriver, a socket for data communication; and BioSpring, a Spring network simulation engine, were extended to perform IMS. These components are designed to easily communicate with each other, adapt to other molecular simulation software, and provide a development framework for adding new interaction models to simulate biological phenomena such as protein alignment in the membrane at a fast enough rate for real-time experiments. (3) Results: We describe in detail the integration of an implicit membrane model for Integral Membrane Protein And Lipid Association (IMPALA) into our IMS framework. Our implementation can cover multiple levels of representation, and the degrees of freedom can be tuned to optimize the experience. We explain the validation of this model in an interactive and exhaustive search mode. (4) Conclusions: Protein positioning in model membranes can now be performed interactively in real time.<\/jats:p>","DOI":"10.3390\/a15110415","type":"journal-article","created":{"date-parts":[[2022,11,8]],"date-time":"2022-11-08T11:31:51Z","timestamp":1667907111000},"page":"415","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Fast and Interactive Positioning of Proteins within Membranes"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2069-4161","authenticated-orcid":false,"given":"Andr\u00e9","family":"Lanrezac","sequence":"first","affiliation":[{"name":"Laboratoire de Biochimie Th\u00e9orique, CNRS, Universit\u00e9 Paris Cit\u00e9, 13 Rue Pierre et Marie Curie, F-75005 Paris, France"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1714-2238","authenticated-orcid":false,"given":"Benoist","family":"Laurent","sequence":"additional","affiliation":[{"name":"Laboratoire de Biochimie Th\u00e9orique, CNRS, Universit\u00e9 Paris Cit\u00e9, 13 Rue Pierre et Marie Curie, F-75005 Paris, France"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6149-9480","authenticated-orcid":false,"given":"Hubert","family":"Santuz","sequence":"additional","affiliation":[{"name":"Laboratoire de Biochimie Th\u00e9orique, CNRS, Universit\u00e9 Paris Cit\u00e9, 13 Rue Pierre et Marie Curie, F-75005 Paris, France"}]},{"given":"Nicolas","family":"F\u00e9rey","sequence":"additional","affiliation":[{"name":"Laboratoire de Biochimie Th\u00e9orique, CNRS, Universit\u00e9 Paris Cit\u00e9, 13 Rue Pierre et Marie Curie, F-75005 Paris, France"},{"name":"Laboratoire Interdisciplinaire des Sciences du Num\u00e9rique, CNRS, Universit\u00e9 Paris-Saclay, 91405 Orsay, France"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6472-0486","authenticated-orcid":false,"given":"Marc","family":"Baaden","sequence":"additional","affiliation":[{"name":"Laboratoire de Biochimie Th\u00e9orique, CNRS, Universit\u00e9 Paris Cit\u00e9, 13 Rue Pierre et Marie Curie, F-75005 Paris, France"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1889","DOI":"10.1016\/j.jmb.2019.02.018","article-title":"Visualizing Biological Membrane Organization and Dynamics","volume":"431","author":"Baaden","year":"2019","journal-title":"J. Mol. Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"D370","DOI":"10.1093\/nar\/gkr703","article-title":"OPM Database and PPM Web Server: Resources for Positioning of Proteins in Membranes","volume":"40","author":"Lomize","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1007\/s00018-007-6439-x","article-title":"The Role of Transmembrane Domains in Membrane Fusion","volume":"64","author":"Langosch","year":"2007","journal-title":"Cell Mol. Life Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1083\/jcb.151.2.425","article-title":"The Transmembrane Domain of Influenza Hemagglutinin Exhibits a Stringent Length Requirement to Support the Hemifusion to Fusion Transition","volume":"151","author":"Armstrong","year":"2000","journal-title":"J. Cell Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1016\/j.bpj.2012.08.007","article-title":"Coarse-Grain Simulations Reveal Movement of the Synaptobrevin C-Terminus in Response to Piconewton Forces","volume":"103","author":"Lindau","year":"2012","journal-title":"Biophys. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e4318","DOI":"10.1002\/pro.4318","article-title":"Membranome 3.0: Database of Single-Pass Membrane Proteins with AlphaFold Models","volume":"31","author":"Lomize","year":"2022","journal-title":"Protein Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1016\/j.str.2015.05.006","article-title":"MemProtMD: Automated Insertion of Membrane Protein Structures into Explicit Lipid Membranes","volume":"23","author":"Stansfeld","year":"2015","journal-title":"Structure"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.1002\/cphc.200900216","article-title":"Coarse-Grain Simulations of the R-SNARE Fusion Protein in Its Membrane Environment Detect Long-Lived Conformational Sub-States","volume":"10","author":"Durrieu","year":"2009","journal-title":"Chemphyschem"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/S1093-3263(03)00122-0","article-title":"Insertion of X-Ray Structures of Proteins in Membranes","volume":"22","author":"Basyn","year":"2003","journal-title":"J. Mol. Graph. Model."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2697","DOI":"10.1021\/ja0569104","article-title":"Insertion and Assembly of Membrane Proteins via Simulation","volume":"128","author":"Bond","year":"2006","journal-title":"J. Am. Chem. Soc."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2169","DOI":"10.1002\/jcc.21507","article-title":"G_membed: Efficient Insertion of a Membrane Protein into an Equilibrated Lipid Bilayer with Minimal Perturbation","volume":"31","author":"Wolf","year":"2010","journal-title":"J. Comput. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e1594","DOI":"10.1002\/wcms.1594","article-title":"Wielding the Power of Interactive Molecular Simulations","volume":"12","author":"Lanrezac","year":"2021","journal-title":"WIREs Comput. Mol. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.csbj.2020.11.052","article-title":"Advances in Integrative Structural Biology: Towards Understanding Protein Complexes in Their Cellular Context","volume":"19","author":"Ziegler","year":"2021","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/S0005-2736(99)00090-5","article-title":"Computational Study of Nisin Interaction with Model Membrane","volume":"1420","author":"Lins","year":"1999","journal-title":"Biochim Biophys. Acta"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1021\/bc990156s","article-title":"Translocation Properties of Novel Cell Penetrating Transportan and Penetratin Analogues","volume":"11","author":"Lindgren","year":"2000","journal-title":"Bioconjugate Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1824","DOI":"10.1021\/bi002019k","article-title":"Translocation of the PAntp Peptide and Its Amphipathic Analogue AP-2AL","volume":"40","author":"Drin","year":"2001","journal-title":"Biochemistry"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/S1093-3263(01)00114-0","article-title":"Prediction of Membrane Protein Orientation in Lipid Bilayers: A Theoretical Approach","volume":"20","author":"Basyn","year":"2001","journal-title":"J. Mol. Graph. Model."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1002\/(SICI)1097-0134(19980301)30:4<357::AID-PROT3>3.0.CO;2-G","article-title":"IMPALA: A Simple Restraint Field to Simulate the Biological Membrane in Molecular Structure Studies","volume":"30","author":"Ducarme","year":"1998","journal-title":"Proteins"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/0926-2040(95)01224-9","article-title":"Orientations of Helical Peptides in Membrane Bilayers by Solid State NMR Spectroscopy","volume":"7","author":"Bechinger","year":"1996","journal-title":"Solid State Nucl. Magn. Reson."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1038\/2983","article-title":"Structure of the Outer Membrane Protein A Transmembrane Domain","volume":"5","author":"Pautsch","year":"1998","journal-title":"Nat. Struct Biol."},{"key":"ref_21","first-page":"369","article-title":"Hydrophobic Parameters Pi of Amino-Acid Side Chains from The Partitioning Of N-Acetyl-Amino Amides","volume":"18","author":"Pliska","year":"1983","journal-title":"Eur. J. Med. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2375","DOI":"10.1002\/jcc.21235","article-title":"Complex Molecular Assemblies at Hand via Interactive Simulations","volume":"30","author":"Delalande","year":"2009","journal-title":"J. Comput. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1107\/S2059798321002941","article-title":"UnityMol Prototype for FAIR Sharing of Molecular-Visualization Experiences: From Pictures in the Cloud to Collaborative Virtual Reality Exploration in Immersive 3D Environments","volume":"77","author":"Martinez","year":"2021","journal-title":"Acta Crystallogr. D Struct. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1039\/C3FD00134B","article-title":"Innovative Interactive Flexible Docking Method for Multi-Scale Reconstruction Elucidates Dystrophin Molecular Assembly","volume":"169","author":"Molza","year":"2014","journal-title":"Faraday Discuss."},{"key":"ref_25","first-page":"20180222","article-title":"Flexibility of Network Materials and the Rigid Unit Mode Model: A Personal Perspective","volume":"377","author":"Dove","year":"2019","journal-title":"Philos. Trans. A Math. Phys. Eng. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1038\/s41592-021-01098-3","article-title":"Martini 3: A General Purpose Force Field for Coarse-Grained Molecular Dynamics","volume":"18","author":"Souza","year":"2021","journal-title":"Nat. Methods"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1002\/jcc.540141103","article-title":"Improved Strategy in Analytic Surface Calculation for Molecular Systems: Handling of Singularities and Computational Efficiency","volume":"14","author":"Eisenhaber","year":"1993","journal-title":"J. Comput. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1002\/jcc.540160303","article-title":"The Double Cubic Lattice Method: Efficient Approaches to Numerical Integration of Surface Area and Volume and to Dot Surface Contouring of Molecular Assemblies","volume":"16","author":"Eisenhaber","year":"1995","journal-title":"J. Comput. Chem."},{"key":"ref_29","unstructured":"Hubbard, S.J., and Thornton, J.M. (1993). \u201cNaccess\u201d, Computer Program, Department of Biochemistry and Molecular Biology, University College London."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"189","DOI":"10.12688\/f1000research.7931.1","article-title":"FreeSASA: An Open Source C Library for Solvent Accessible Surface Area Calculations","volume":"5","author":"Mitternacht","year":"2016","journal-title":"F1000Res"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2577","DOI":"10.1002\/bip.360221211","article-title":"Dictionary of Protein Secondary Structure: Pattern Recognition of Hydrogen-Bonded and Geometrical Features","volume":"22","author":"Kabsch","year":"1983","journal-title":"Biopolymers"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Liu, L., and \u00d6zsu, M.T. (2009). Linking and Brushing. Encyclopedia of Database Systems, Springer US.","DOI":"10.1007\/978-0-387-39940-9"},{"key":"ref_33","unstructured":"Rohatgi, A. (2022, November 01). Webplotdigitizer: Version 4.6 2022. Available online: https:\/\/automeris.io\/WebPlotDigitizer\/."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2942","DOI":"10.1529\/biophysj.104.046987","article-title":"OmpT: Molecular Dynamics Simulations of an Outer Membrane Enzyme","volume":"87","author":"Baaden","year":"2004","journal-title":"Biophys. J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/s00249-007-0185-8","article-title":"Outer Membrane Proteins: Comparing X-Ray and NMR Structures by MD Simulations in Lipid Bilayers","volume":"37","author":"Cox","year":"2008","journal-title":"Eur. Biophys. J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/j.str.2016.02.014","article-title":"Sites of Anesthetic Inhibitory Action on a Cationic Ligand-Gated Ion Channel","volume":"24","author":"Laurent","year":"2016","journal-title":"Structure"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1007\/s10858-011-9523-3","article-title":"Electrostatically-Driven Fast Association and Perdeuteration Allow Detection of Transferred Cross-Relaxation for G Protein-Coupled Receptor Ligands with Equilibrium Dissociation Constants in the High-to-Low Nanomolar Range","volume":"50","author":"Catoire","year":"2011","journal-title":"J. Biomol. NMR"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Papin, J.A., Mac Gabhann, F., Sauro, H.M., Nickerson, D., and Rampadarath, A. (2020). Improving Reproducibility in Computational Biology Research. PLoS Comput. Biol., 16.","DOI":"10.1371\/journal.pcbi.1007881"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"6947","DOI":"10.1038\/s41467-021-27222-7","article-title":"Ensuring Scientific Reproducibility in Bio-Macromolecular Modeling via Extensive, Automated Benchmarks","volume":"12","author":"Lyskov","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1080\/07391102.2012.712459","article-title":"Elucidation by NMR Solution of Neurotensin in Small Unilamellar Vesicle Environment: Molecular Surveys for Neurotensin Receptor Recognition","volume":"31","author":"Bondon","year":"2013","journal-title":"J. Biomol. Struct. Dyn."}],"container-title":["Algorithms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4893\/15\/11\/415\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:11:46Z","timestamp":1760145106000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4893\/15\/11\/415"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,7]]},"references-count":40,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["a15110415"],"URL":"https:\/\/doi.org\/10.3390\/a15110415","relation":{},"ISSN":["1999-4893"],"issn-type":[{"type":"electronic","value":"1999-4893"}],"subject":[],"published":{"date-parts":[[2022,11,7]]}}}