{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T03:20:25Z","timestamp":1780975225168,"version":"3.54.1"},"reference-count":142,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,10,10]],"date-time":"2023-10-10T00:00:00Z","timestamp":1696896000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Kay Family Foundation","award":["A20-0032"],"award-info":[{"award-number":["A20-0032"]}]},{"name":"Kay Family Foundation","award":["R15GM122013"],"award-info":[{"award-number":["R15GM122013"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["A20-0032"],"award-info":[{"award-number":["A20-0032"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R15GM122013"],"award-info":[{"award-number":["R15GM122013"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>In the current study, we explore coarse-grained simulations and atomistic molecular dynamics together with binding energetics scanning and cryptic pocket detection in a comparative examination of conformational landscapes and systematic characterization of allosteric binding sites in the SARS-CoV-2 Omicron BA.2, BA.2.75 and XBB.1 spike full-length trimer complexes with the host receptor ACE2. Microsecond simulations, Markov state models and mutational scanning of binding energies of the SARS-CoV-2 BA.2 and BA.2.75 receptor binding domain complexes revealed the increased thermodynamic stabilization of the BA.2.75 variant and significant dynamic differences between these Omicron variants. Molecular simulations of the SARS-CoV-2 Omicron spike full-length trimer complexes with the ACE2 receptor complemented atomistic studies and enabled an in-depth analysis of mutational and binding effects on conformational dynamic and functional adaptability of the Omicron variants. Despite considerable structural similarities, Omicron variants BA.2, BA.2.75 and XBB.1 can induce unique conformational dynamic signatures and specific distributions of the conformational states. Using conformational ensembles of the SARS-CoV-2 Omicron spike trimer complexes with ACE2, we conducted a comprehensive cryptic pocket screening to examine the role of Omicron mutations and ACE2 binding on the distribution and functional mechanisms of the emerging allosteric binding sites. This analysis captured all experimentally known allosteric sites and discovered networks of inter-connected and functionally relevant allosteric sites that are governed by variant-sensitive conformational adaptability of the SARS-CoV-2 spike structures. The results detailed how ACE2 binding and Omicron mutations in the BA.2, BA.2.75 and XBB.1 spike complexes modulate the distribution of conserved and druggable allosteric pockets harboring functionally important regions. The results are significant for understanding the functional roles of druggable cryptic pockets that can be used for allostery-mediated therapeutic intervention targeting conformational states of the Omicron variants.<\/jats:p>","DOI":"10.3390\/v15102073","type":"journal-article","created":{"date-parts":[[2023,10,10]],"date-time":"2023-10-10T10:23:42Z","timestamp":1696933422000},"page":"2073","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Comparative Analysis of Conformational Dynamics and Systematic Characterization of Cryptic Pockets in the SARS-CoV-2 Omicron BA.2, BA.2.75 and XBB.1 Spike Complexes with the ACE2 Host Receptor: Confluence of Binding and Structural Plasticity in Mediating Networks of Conserved Allosteric Sites"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-3504-6386","authenticated-orcid":false,"given":"Mohammed","family":"Alshahrani","sequence":"first","affiliation":[{"name":"Keck Center for Science and Engineering, Graduate Program in Computational and Data Sciences, Schmid College of Science and Technology, Chapman University, Orange, CA 92866, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace","family":"Gupta","sequence":"additional","affiliation":[{"name":"Keck Center for Science and Engineering, Graduate Program in Computational and Data Sciences, Schmid College of Science and Technology, Chapman University, Orange, CA 92866, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3451-5227","authenticated-orcid":false,"given":"Sian","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Center for Research Computing, Center for Drug Discovery, Design, and Delivery (CD4), Southern Methodist University, Dallas, TX 75275, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Tao","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Center for Research Computing, Center for Drug Discovery, Design, and Delivery (CD4), Southern Methodist University, Dallas, TX 75275, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4507-4471","authenticated-orcid":false,"given":"Gennady","family":"Verkhivker","sequence":"additional","affiliation":[{"name":"Keck Center for Science and Engineering, Graduate Program in Computational and Data Sciences, Schmid College of Science and Technology, Chapman University, Orange, CA 92866, USA"},{"name":"Department of Biomedical and Pharmaceutical Sciences, Chapman University School of Pharmacy, Irvine, CA 92618, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1126\/science.abd4251","article-title":"Distinct conformational states of SARS-CoV-2 spike protein","volume":"369","author":"Cai","year":"2020","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1038\/s41594-020-0479-4","article-title":"Controlling the SARS-CoV-2 spike glycoprotein conformation","volume":"27","author":"Henderson","year":"2020","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1126\/science.abg4493","article-title":"The emerging plasticity of SARS-CoV-2","volume":"371","author":"McCormick","year":"2021","journal-title":"Science"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Ghimire, D., Han, Y., and Lu, M. (2022). Structural Plasticity and Immune Evasion of SARS-CoV-2 Spike Variants. Viruses, 14.","DOI":"10.3390\/v14061255"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"eabe5575","DOI":"10.1126\/sciadv.abe5575","article-title":"Conformational dynamics of SARS-CoV-2 trimeric spike glycoprotein in complex with receptor ACE2 revealed by cryo-EM","volume":"7","author":"Xu","year":"2021","journal-title":"Sci. Adv."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/s41586-020-2772-0","article-title":"Receptor binding and priming of the spike protein of SARS-CoV-2 for membrane fusion","volume":"588","author":"Benton","year":"2020","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1126\/science.abd5223","article-title":"In situ structural analysis of SARS-CoV-2 spike reveals flexibility mediated by three hinges","volume":"370","author":"Sikora","year":"2020","journal-title":"Science"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1016\/j.chom.2020.11.001","article-title":"Real-time conformational dynamics of SARS-CoV-2 spikes on virus particles","volume":"28","author":"Lu","year":"2020","journal-title":"Cell Host Microbe."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Yang, Z., Han, Y., Ding, S., Shi, W., Zhou, T., Finzi, A., Kwong, P.D., Mothes, W., and Lu, M. (2022). SARS-CoV-2 Variants Increase Kinetic Stability of Open Spike Conformations as an Evolutionary Strategy. mBio, 13.","DOI":"10.1128\/mbio.03227-21"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e75433","DOI":"10.7554\/eLife.75433","article-title":"Conformational dynamics and allosteric modulation of the SARS-CoV-2 spike","volume":"11","author":"Li","year":"2022","journal-title":"eLife"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1038\/s41586-022-04581-9","article-title":"Molecular basis of receptor binding and antibody neutralization of Omicron","volume":"604","author":"Hong","year":"2022","journal-title":"Nature"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2050","DOI":"10.1016\/j.molcel.2022.03.028","article-title":"Structural Diversity of the SARS-CoV-2 Omicron Spike","volume":"82","author":"Gobeil","year":"2022","journal-title":"Mol. Cell"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1016\/j.cell.2022.01.019","article-title":"Structural and functional characterizations of infectivity and immune evasion of SARS-CoV-2 Omicron","volume":"185","author":"Cui","year":"2022","journal-title":"Cell"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"eabn8897","DOI":"10.1126\/science.abn8897","article-title":"Structural basis for potent antibody neutralization of SARS-CoV-2 variants including B.1.1.529","volume":"376","author":"Zhou","year":"2022","journal-title":"Science"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"110770","DOI":"10.1016\/j.celrep.2022.110770","article-title":"Structures of Omicron Spike Complexes and Implications for Neutralizing Antibody Development","volume":"39","author":"Guo","year":"2022","journal-title":"Cell Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"111009","DOI":"10.1016\/j.celrep.2022.111009","article-title":"Cryo-EM Structures of SARS-CoV-2 Omicron BA.2 Spike","volume":"39","author":"Stalls","year":"2022","journal-title":"Cell Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1038\/s41392-022-00914-2","article-title":"Characterization of SARS-CoV-2 Omicron Spike RBD Reveals Significantly Decreased Stability, Severe Evasion of Neutralizing-Antibody Recognition but Unaffected Engagement by Decoy ACE2 Modified for Enhanced RBD Binding","volume":"7","author":"Lin","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"110428","DOI":"10.1016\/j.celrep.2022.110428","article-title":"Cryo-EM Structure of the SARS-CoV-2 Omicron Spike","volume":"38","author":"Cerutti","year":"2022","journal-title":"Cell Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1038\/s41467-022-28882-9","article-title":"Cryo-EM Structure of a SARS-CoV-2 Omicron Spike Protein Ectodomain","volume":"13","author":"Ye","year":"2022","journal-title":"Nat Commun."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1038\/s41467-022-28324-6","article-title":"Structural and biochemical rationale for enhanced spike protein fitness in delta and kappa SARS-CoV-2 variants","volume":"13","author":"Saville","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2952","DOI":"10.1016\/j.cell.2022.06.023","article-title":"Structural basis of human ACE2 higher binding affinity to currently circulating Omicron SARS-CoV-2 sub-variants BA.2 and BA.1.1","volume":"185","author":"Li","year":"2022","journal-title":"Cell"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1038\/s41422-022-00672-4","article-title":"Structural and biochemical mechanism for increased infectivity and immune evasion of Omicron BA.2 variant compared to BA.1 and their possible mouse origins","volume":"32","author":"Xu","year":"2022","journal-title":"Cell Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1038\/s41594-023-01023-6","article-title":"Structural and Functional Characteristics of the SARS-CoV-2 Omicron Subvariant BA.2 Spike Protein","volume":"30","author":"Zhang","year":"2023","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1038\/s41586-022-04980-y","article-title":"BA.2.12.1, BA.4 and BA.5 Escape Antibodies Elicited by Omicron Infection","volume":"608","author":"Cao","year":"2022","journal-title":"Nature"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1016\/j.chom.2022.09.018","article-title":"Characterization of the Enhanced Infectivity and Antibody Evasion of Omicron BA.2.75","volume":"30","author":"Cao","year":"2022","journal-title":"Cell Host Microbe"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e28539","DOI":"10.1002\/jmv.28539","article-title":"Emerging Omicron Subvariants Evade Neutralizing Immunity Elicited by Vaccine or BA.1\/BA.2 Infection","volume":"95","author":"Chen","year":"2023","journal-title":"J. Med. Virol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1016\/j.chom.2022.10.003","article-title":"Virological Characteristics of the SARS-CoV-2 Omicron BA.2.75 Variant","volume":"30","author":"Saito","year":"2022","journal-title":"Cell Host Microbe"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1016\/j.chom.2022.09.015","article-title":"Evasion of Neutralizing Antibody Responses by the SARS-CoV-2 BA.2.75 Variant","volume":"30","author":"Qu","year":"2022","journal-title":"Cell Host Microbe"},{"key":"ref_29","first-page":"521","article-title":"Imprinted SARS-CoV-2 Humoral Immunity Induces Convergent Omicron RBD Evolution","volume":"614","author":"Cao","year":"2023","journal-title":"Nature"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.cell.2022.12.018","article-title":"Alarming Antibody Evasion Properties of Rising SARS-CoV-2 BQ and XBB Subvariants","volume":"186","author":"Wang","year":"2023","journal-title":"Cell"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2800","DOI":"10.1038\/s41467-023-38435-3","article-title":"Virological Characteristics of the SARS-CoV-2 XBB Variant Derived from Recombination of Two Omicron Subvariants","volume":"14","author":"Tamura","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/S1473-3099(23)00010-5","article-title":"ACE2 Binding and Antibody Evasion in Enhanced Transmissibility of XBB.1.5","volume":"23","author":"Yue","year":"2023","journal-title":"Lancet Infect. Dis."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1038\/s41423-023-00988-0","article-title":"Profound Neutralization Evasion and Augmented Host Cell Entry Are Hallmarks of the Fast-Spreading SARS-CoV-2 Lineage XBB.1.5","volume":"20","author":"Hoffmann","year":"2023","journal-title":"Cell Mol. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1038\/s41594-022-00735-5","article-title":"The SARS-CoV-2 Spike Reversibly Samples an Open-Trimer Conformation Exposing Novel Epitopes","volume":"29","author":"Costello","year":"2022","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1038\/s41467-023-36745-0","article-title":"Structural Dynamics in the Evolution of SARS-CoV-2 Spike Glycoprotein","volume":"14","author":"Calvaresi","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e82584","DOI":"10.7554\/eLife.82584","article-title":"Timeline of Changes in Spike Conformational Dynamics in Emergent SARS-CoV-2 Variants Reveal Progressive Stabilization of Trimer Stalk with Altered NTD Dynamics","volume":"12","author":"Braet","year":"2023","journal-title":"eLife"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e63646","DOI":"10.7554\/eLife.63646","article-title":"SARS-CoV-2 S Protein:ACE2 Interaction Reveals Novel Allosteric Targets","volume":"10","author":"Raghuvamsi","year":"2021","journal-title":"eLife"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1021\/acsinfecdis.3c00010","article-title":"hACE2-Induced Allosteric Activation in SARS-CoV versus SARS-CoV-2 Spike Assemblies Revealed by Structural Dynamics","volume":"9","author":"Chen","year":"2023","journal-title":"ACS Infect Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1126\/science.abd3255","article-title":"Free Fatty Acid Binding Pocket in the Locked Structure of SARS-CoV-2 Spike Protein","volume":"370","author":"Toelzer","year":"2020","journal-title":"Science"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1107\/S2059798323000049","article-title":"Cryo-EM Reveals Binding of Linoleic Acid to SARS-CoV-2 Spike Glycoprotein, Suggesting an Antiviral Treatment Strategy","volume":"79","author":"Toelzer","year":"2023","journal-title":"Acta Crystallogr D Struct Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"eadc9179","DOI":"10.1126\/sciadv.adc9179","article-title":"The Free Fatty Acid\u2013Binding Pocket Is a Conserved Hallmark in Pathogenic \u03b2-Coronavirus Spike Proteins from SARS-CoV to Omicron","volume":"8","author":"Toelzer","year":"2022","journal-title":"Sci. Adv."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/s41392-023-01534-0","article-title":"Defining a Highly Conserved Cryptic Epitope for Antibody Recognition of SARS-CoV-2 Variants","volume":"8","author":"Hao","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1126\/science.abe1502","article-title":"Structural Analysis of Full-Length SARS-CoV-2 Spike Protein from an Advanced Vaccine Candidate","volume":"370","author":"Bangaru","year":"2020","journal-title":"Science"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"eabg7607","DOI":"10.1126\/sciadv.abg7607","article-title":"SARS-CoV-2 Can Recruit a Heme Metabolite to Evade Antibody Immunity","volume":"7","author":"Rosa","year":"2021","journal-title":"Sci. Adv."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Altomare, C.G., Adelsberg, D.C., Carreno, J.M., Sapse, I.A., Amanat, F., Ellebedy, A.H., Simon, V., Krammer, F., and Bajic, G. (2022). Structure of a Vaccine-Induced, Germline-Encoded Human Antibody Defines a Neutralizing Epitope on the SARS-CoV-2 Spike N-Terminal Domain. mBio, 13.","DOI":"10.1128\/mbio.03580-21"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e83710","DOI":"10.7554\/eLife.83710","article-title":"Identification of a Conserved S2 Epitope Present on Spike Proteins from All Highly Pathogenic Coronaviruses","volume":"12","author":"Silva","year":"2023","journal-title":"eLife"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Gan, H.H., Twaddle, A., Marchand, B., and Gunsalus, K.C. (2021). Structural Modeling of the SARS-CoV-2 Spike\/Human ACE2 Complex Interface can Identify High-Affinity Variants Associated with Increased Transmissibility. J. Mol. Biol., 433.","DOI":"10.1016\/j.jmb.2021.167051"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"894531","DOI":"10.3389\/fviro.2022.894531","article-title":"Omicron Spike Protein Has a Positive Electrostatic Surface That Promotes ACE2 Recognition and Antibody Escape","volume":"2","author":"Gan","year":"2022","journal-title":"Front. Virol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"6835","DOI":"10.1021\/acs.jpcb.2c04225","article-title":"Electrostatic Features for the Receptor Binding Domain of SARS-CoV-2 Wildtype and Its Variants. Compass to the Severity of the Future Variants with the Charge-Rule","volume":"126","author":"Giron","year":"2022","journal-title":"J. Phys. Chem. B."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Hristova, S.H., and Zhivkov, A.M. (2023). Omicron Coronavirus: pH-Dependent Electrostatic Potential and Energy of Association of Spike Protein to ACE2 Receptor. Viruses, 15.","DOI":"10.3390\/v15081752"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e28119","DOI":"10.1002\/jmv.28119","article-title":"On the SARS-CoV-2 BA.2.75 Variant: A Genetic and Structural Point of View","volume":"95","author":"Scarpa","year":"2023","journal-title":"J. Med. Virol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1002\/jmv.27528","article-title":"The Electrostatic Potential of the Omicron Variant Spike Is Higher than in Delta and Delta-plus Variants: A Hint to Higher Transmissibility?","volume":"94","author":"Pascarella","year":"2022","journal-title":"J. Med. Virol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e62","DOI":"10.1016\/j.jinf.2022.02.023","article-title":"The Value of Electrostatic Potentials of the Spike Receptor Binding and N-Terminal Domains in Addressing Transmissibility and Infectivity of SARS-CoV-2 Variants of Concern","volume":"84","author":"Pascarella","year":"2022","journal-title":"J Infect."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Barre, A., Klonjkowski, B., Benoist, H., and Roug\u00e9, P. (2022). How Do Point Mutations Enhancing the Basic Character of the RBDs of SARS-CoV-2 Variants Affect Their Transmissibility and Infectivity Capacities?. Viruses, 14.","DOI":"10.3390\/v14040783"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Verkhivker, G., Alshahrani, M., and Gupta, G. (2023). Coarse-Grained Molecular Simulations and Ensemble-Based Mutational Profiling of Protein Stability in the Different Functional Forms of the SARS-CoV-2 Spike Trimers: Balancing Stability and Adaptability in BA.1, BA.2 and BA.2.75 Variants. Int. J. Mol. Sci., 24.","DOI":"10.1101\/2023.02.28.530489"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.1073\/pnas.1908898117","article-title":"Cryo-EM analysis of a feline coronavirus spike protein reveals a unique structure and camouflaging glycans","volume":"117","author":"Yang","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2688","DOI":"10.1038\/s41467-020-16567-0","article-title":"Vulnerabilities in coronavirus glycan shields despite extensive glycosylation","volume":"11","author":"Watanabe","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1126\/science.abb9983","article-title":"Site-specific glycan analysis of the SARS-CoV-2 spike","volume":"369","author":"Watanabe","year":"2020","journal-title":"Science"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1039\/D1SC04832E","article-title":"Fine-Tuning the Spike: Role of the Nature and Topology of the Glycan Shield in the Structure and Dynamics of the SARS-CoV-2 S","volume":"13","author":"Harbison","year":"2022","journal-title":"Chem. Sci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1016\/j.chom.2020.08.004","article-title":"Virus-receptor interactions of glycosylated SARS-CoV-2 spike and human ACE2 receptor","volume":"28","author":"Zhao","year":"2020","journal-title":"Cell Host Microbe"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1021\/acscentsci.0c01056","article-title":"Beyond shielding: The roles of glycans in the SARS-CoV-2 spike potein","volume":"6","author":"Casalino","year":"2020","journal-title":"ACS Cent. Sci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1016\/j.bpj.2020.10.036","article-title":"The Flexibility of ACE2 in the Context of SARS-CoV-2 Infection","volume":"120","author":"Barros","year":"2021","journal-title":"Biophys J."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"e2100425118","DOI":"10.1073\/pnas.2100425118","article-title":"Dual Nature of Human ACE2 Glycosylation in Binding to SARS-CoV-2 Spike","volume":"118","author":"Mehdipour","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"von B\u00fclow, S., Sikora, M., Blanc, F.E.C., Covino, R., and Hummer, G. (2023). Antibody accessibility determines location of spike surface mutations in SARS-CoV-2 variants. PLoS Comput. Biol., 19.","DOI":"10.1371\/journal.pcbi.1010822"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1038\/s41557-021-00707-0","article-title":"SARS-CoV-2 simulations go exascale to predict dramatic spike opening and cryptic pockets across the proteome","volume":"13","author":"Zimmerman","year":"2021","journal-title":"Nat. Chem."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Pang, Y.T., Acharya, A., Lynch, D.L., Pavlova, A., and Gumbart, J.C. (2022). SARS-CoV-2 Spike Opening Dynamics and Energetics Reveal the Individual Roles of Glycans and Their Collective Impact. Commun. Biol., 5.","DOI":"10.1038\/s42003-022-04138-6"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1016\/j.bpj.2021.01.012","article-title":"Elucidation of Interactions Regulating Conformational Stability and Dynamics of SARS-CoV-2 S-Protein","volume":"120","author":"Mori","year":"2021","journal-title":"Biophys J."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1016\/j.str.2022.05.006","article-title":"Uncovering Cryptic Pockets in the SARS-CoV-2 Spike Glycoprotein","volume":"30","author":"Zuzic","year":"2022","journal-title":"Structure"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2339","DOI":"10.1016\/j.csbj.2023.03.029","article-title":"Identifying Promising Druggable Binding Sites and Their Flexibility to Target the Receptor-Binding Domain of SARS-CoV-2 Spike Protein","volume":"21","author":"Ghoula","year":"2023","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Verkhivker, G., Agajanian, S., Kassab, R., and Krishnan, K. (2022). Probing Mechanisms of Binding and Allostery in the SARS-CoV-2 Spike Omicron Variant Complexes with the Host Receptor: Revealing Functional Roles of the Binding Hotspots in Mediating Epistatic Effects and Communication with Allosteric Pockets. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231911542"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2827","DOI":"10.1021\/acs.jmedchem.1c00320","article-title":"Probing the Allosteric Inhibition Mechanism of a Spike Protein Using Molecular Dynamics Simulations and Active Compound Identifications","volume":"65","author":"Wang","year":"2021","journal-title":"J. Med. Chem."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"659764","DOI":"10.3389\/fchem.2021.659764","article-title":"Identification of Potential Binding Sites of Sialic Acids on the RBD Domain of SARS-CoV-2 Spike Protein","volume":"9","author":"Li","year":"2021","journal-title":"Front. Chem."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/s41392-023-01472-x","article-title":"Targetable Elements in SARS-CoV-2 S2 Subunit for the Design of Pan-Coronavirus Fusion Inhibitors and Vaccines","volume":"8","author":"Guo","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Xing, L., Xu, X., Xu, W., Liu, Z., Shen, X., Zhou, J., Xu, L., Pu, J., Yang, C., and Huang, Y. (2022). A Five-Helix-Based SARS-CoV-2 Fusion Inhibitor Targeting Heptad Repeat 2 Domain against SARS-CoV-2 and Its Variants of Concern. Viruses, 14.","DOI":"10.3390\/v14030597"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"e00194-21","DOI":"10.1128\/JVI.00194-21","article-title":"Cryo-Electron Microscopy Structure of S-Trimer, a Subunit Vaccine Candidate for COVID-19","volume":"95","author":"Ma","year":"2021","journal-title":"J Virol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"111903","DOI":"10.1016\/j.celrep.2022.111903","article-title":"A Delicate Balance between Antibody Evasion and ACE2 Affinity for Omicron BA.2.75","volume":"42","author":"Huo","year":"2023","journal-title":"Cell Rep."},{"key":"ref_77","first-page":"D271","article-title":"The RCSB protein data bank: Integrative view of protein, gene and 3D structural information","volume":"45","author":"Rose","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"W719","DOI":"10.1093\/nar\/gkq453","article-title":"WIWS: A protein structure bioinformatics web service collection","volume":"38","author":"Hekkelman","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"W173","DOI":"10.1093\/nar\/gkl113","article-title":"ArchPRED: A template based loop structure prediction server","volume":"34","author":"Zhai","year":"2006","journal-title":"Nucleic Acids Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1002\/prot.22488","article-title":"Improved prediction of protein side-chain conformations with SCWRL4","volume":"77","author":"Krivov","year":"2009","journal-title":"Proteins"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"2284","DOI":"10.1021\/ct200133y","article-title":"Improved treatment of ligands and coupling effects in empirical calculation and rationalization of pKa values","volume":"7","author":"Olsson","year":"2011","journal-title":"J. Chem. Theory Comput."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1021\/ct100578z","article-title":"PROPKA3: Consistent treatment of internal and surface residues in empirical pKa predictions","volume":"7","author":"Olsson","year":"2011","journal-title":"J. Chem. Theory Comput."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"W406","DOI":"10.1093\/nar\/gkw336","article-title":"3Drefine: An Interactive Web Server for Efficient Protein Structure Refinement","volume":"44","author":"Bhattacharya","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1038\/nmeth.4067","article-title":"CHARMM36m: An improved force field for folded and intrinsically disordered proteins","volume":"14","author":"Huang","year":"2017","journal-title":"Nat. Methods"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1063\/1.445869","article-title":"Comparison of Simple Potential Functions for Simulating Liquid Water","volume":"79","author":"Jorgensen","year":"1983","journal-title":"J. Chem. Phys."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"6673","DOI":"10.1021\/acs.jpcb.8b02144","article-title":"Validating Molecular Dynamics Simulations against Experimental Observables in Light of Underlying Conformational Ensembles","volume":"122","author":"Childers","year":"2018","journal-title":"J. Phys. Chem. B."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"5957","DOI":"10.33011\/livecoms.1.1.5957","article-title":"Best Practices for Foundations in Molecular Simulations [Article v1.0]","volume":"1","author":"Braun","year":"2019","journal-title":"Living J. Comput. Mol. Sci."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"120116","DOI":"10.1016\/j.molliq.2022.120116","article-title":"Effects of Thermostats\/Barostats on Physical Properties of Liquids by Molecular Dynamics Simulations","volume":"365","author":"Ke","year":"2022","journal-title":"J. Mol. Liq."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/0021-9991(77)90098-5","article-title":"Numerical Integration of the Cartesian Equations of Motion of a System with Constraints: Molecular Dynamics of n-Alkanes","volume":"23","author":"Ryckaert","year":"1977","journal-title":"J. Comput. Phys."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"5624","DOI":"10.1021\/acs.jctc.5b00648","article-title":"A Stochastic Algorithm for the Isobaric-Isothermal Ensemble with Ewald Summations for All Long Range Forces","volume":"11","author":"Elber","year":"2015","journal-title":"J. Chem. Theory Comput."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Eastman, P., Swails, J., Chodera, J.D., McGibbon, R.T., Zhao, Y., Beauchamp, K.A., Wang, L.-P., Simmonett, A.C., Harrigan, M.P., and Stern, C.D. (2017). OpenMM 7: Rapid Development of High Performance Algorithms for Molecular Dynamics. PLoS Comput. Biol., 13.","DOI":"10.1371\/journal.pcbi.1005659"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1016\/j.bpj.2015.08.015","article-title":"MDTraj: A Modern Open Library for the Analysis of Molecular Dynamics Trajectories","volume":"109","author":"McGibbon","year":"2015","journal-title":"Biophys. J."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Haque, I.S., Beauchamp, K.A., and Pande, V.S. (2014). A Fast 3 \u00d7 N Matrix Multiply Routine for Calculation of Protein RMSD. bioRxiv.","DOI":"10.1101\/008631"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1107\/S0108767305015266","article-title":"Rapid Calculation of RMSDs Using a Quaternion-Based Characteristic Polynomial","volume":"61","author":"Theobald","year":"2005","journal-title":"Acta Crystallogr. A."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1002\/jcc.21439","article-title":"Fast Determination of the Optimal Rotational Matrix for Macromolecular Superpositions","volume":"31","author":"Liu","year":"2010","journal-title":"J. Comput. Chem."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"065101","DOI":"10.1063\/1.3554380","article-title":"Slow Dynamics in Protein Fluctuations Revealed by Time-Structure Based Independent Component Analysis: The Case of Domain Motions","volume":"134","author":"Naritomi","year":"2011","journal-title":"J. Chem. Phys."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2000","DOI":"10.1021\/ct300878a","article-title":"Improvements in Markov State Model Construction Reveal Many Non-Native Interactions in the Folding of NTL9","volume":"9","author":"Schwantes","year":"2013","journal-title":"J. Chem. Theory Comput."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"2440","DOI":"10.1021\/acs.jctc.7b00182","article-title":"tICA-Metadynamics: Accelerating Metadynamics by Using Kinetically Selected Collective Variables","volume":"13","author":"Sultan","year":"2017","journal-title":"J. Chem. Theory Comput."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"5022","DOI":"10.1021\/acs.jpcb.1c02081","article-title":"UMAP as a Dimensionality Reduction Tool for Molecular Dynamics Simulations of Biomacromolecules: A Comparison Study","volume":"125","author":"Trozzi","year":"2021","journal-title":"J. Phys. Chem. B."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"5525","DOI":"10.1021\/acs.jctc.5b00743","article-title":"PyEMMA 2: A Software Package for Estimation, Validation, and Analysis of Markov Models","volume":"11","author":"Scherer","year":"2015","journal-title":"J. Chem. Theory Comput."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"E3221","DOI":"10.1073\/pnas.1525092113","article-title":"Multiensemble Markov models of molecular thermodynamics and kinetics","volume":"113","author":"Wu","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"3473","DOI":"10.1021\/acs.jctc.6b00339","article-title":"Accurate Estimation of Protein Folding and Unfolding Times: Beyond Markov State Models","volume":"12","author":"Adelman","year":"2016","journal-title":"J. Chem. Theory Comput."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2734","DOI":"10.1073\/pnas.1417811112","article-title":"Discovery of multiple hidden allosteric sites by combining Markov state models and experiments","volume":"112","author":"Bowman","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Bowman, G.R., and No\u00e9, F. (2014). Software for Building Markov State Models. Adv. Exp. Med. Biol., 797.","DOI":"10.1007\/978-94-007-7606-7_11"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1007\/978-1-62703-658-0_8","article-title":"A Tutorial on Building Markov State Models with MSMBuilder and Coarse-Graining Them with BACE","volume":"1084","author":"Bowman","year":"2014","journal-title":"Methods Mol Biol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"174101","DOI":"10.1063\/1.4934536","article-title":"Estimation and Uncertainty of Reversible Markov Models","volume":"143","author":"Wu","year":"2015","journal-title":"J. Chem. Phys."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.ymeth.2009.04.013","article-title":"Using Generalized Ensemble Simulations and Markov State Models to Identify Conformational States","volume":"49","author":"Bowman","year":"2009","journal-title":"Methods"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"2706","DOI":"10.1529\/biophysj.105.074997","article-title":"Investigating the local flexibility of functional residues in hemoproteins","volume":"90","author":"Lavery","year":"2006","journal-title":"Biophys. J."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1002\/prot.21353","article-title":"Locating the active sites of enzymes using mechanical properties","volume":"67","author":"Laforet","year":"2007","journal-title":"Proteins"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/bs.mie.2016.05.022","article-title":"Bridging Enzymatic Structure Function via Mechanics: A Coarse-Grain Approach","volume":"578","year":"2016","journal-title":"Methods Enzymol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1352","DOI":"10.1063\/1.436761","article-title":"Brownian dynamics with hydrodynamic interactions","volume":"69","author":"Ermak","year":"1978","journal-title":"J. Chem. Phys."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1063\/1.455218","article-title":"Brownian dynamics simulation of a lipid chain in a membrane bilayer","volume":"89","author":"Pastor","year":"1988","journal-title":"J. Chem. Phys."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1002\/jcc.20906","article-title":"Fast procedure for reconstruction of full-atom protein models from reduced representations","volume":"29","author":"Rotkiewicz","year":"2008","journal-title":"J. Comput. Chem."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1093\/bioinformatics\/btv740","article-title":"CG2AA: Backmapping protein coarse-grained structures","volume":"32","author":"Lombardi","year":"2016","journal-title":"Bioinformatics"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"W333","DOI":"10.1093\/nar\/gkt450","article-title":"BeAtMuSiC: Prediction of changes in protein-protein binding affinity on mutations","volume":"41","author":"Dehouck","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"4010","DOI":"10.1529\/biophysj.105.079434","article-title":"A new generation of statistical potentials for proteins","volume":"90","author":"Dehouck","year":"2006","journal-title":"Biophys. J."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"2537","DOI":"10.1093\/bioinformatics\/btp445","article-title":"Fast and accurate predictions of protein stability changes upon mutations using statistical potentials and neural networks: PoPMuSiC-2.0","volume":"25","author":"Dehouck","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s13321-018-0285-8","article-title":"P2Rank: Machine Learning Based Tool for Rapid and Accurate Prediction of Ligand Binding Sites from Protein Structure","volume":"10","author":"Hoksza","year":"2018","journal-title":"J. Cheminform."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"W593","DOI":"10.1093\/nar\/gkac389","article-title":"PrankWeb 3: Accelerated Ligand-Binding Site Predictions for Experimental and Modelled Protein Structures","volume":"50","author":"Jakubec","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Le Guilloux, V., Schmidtke, P., and Tuffery, P. (2009). Fpocket: An Open Source Platform for Ligand Pocket Detection. BMC Bioinform., 10.","DOI":"10.1186\/1471-2105-10-168"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"3185","DOI":"10.1093\/bioinformatics\/btp562","article-title":"EasyMIFS and SiteHound: A toolkit for the identification of ligand-binding sites in protein structures","volume":"25","author":"Ghersi","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"2083","DOI":"10.1093\/bioinformatics\/btr331","article-title":"Identification of Cavities on Protein Surface Using Multiple Computational Approaches for Drug Binding Site Prediction","volume":"27","author":"Zhang","year":"2011","journal-title":"Bioinformatics"},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Xiao, S., Tian, H., and Tao, P. (2022). PASSer2.0: Accurate Prediction of Protein Allosteric Sites Through Automated Machine Learning. Front. Mol. Biosci., 9.","DOI":"10.3389\/fmolb.2022.879251"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"W427","DOI":"10.1093\/nar\/gkad303","article-title":"PASSer: Fast and Accurate Prediction of Protein Allosteric Sites","volume":"51","author":"Tian","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"2223","DOI":"10.1002\/jcc.27193","article-title":"PASSerRank: Prediction of allosteric sites with learning to rank","volume":"44","author":"Tian","year":"2023","journal-title":"J. Comput. Chem."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"2117","DOI":"10.1016\/j.csbj.2020.07.017","article-title":"Unlocking COVID Therapeutic Targets: A Structure-Based Rationale against SARS-CoV-2, SARS-CoV and MERS-CoV Spike","volume":"18","author":"Correia","year":"2020","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"572885","DOI":"10.3389\/fchem.2020.572885","article-title":"Hijacking SARS-CoV-2\/ACE2 Receptor Interaction by Natural and Semi-Synthetic Steroidal Agents Acting on Functional Pockets on the Receptor Binding Domain","volume":"8","author":"Carino","year":"2020","journal-title":"Front Chem."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"2074","DOI":"10.1093\/bioinformatics\/bts310","article-title":"DoGSiteScorer: A Web Server for Automatic Binding Site Prediction, Analysis and Druggability Assessment","volume":"28","author":"Volkamer","year":"2012","journal-title":"Bioinformatics"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1021\/ci5006004","article-title":"PockDrug: A Model for Predicting Pocket Druggability That Overcomes Pocket Estimation Uncertainties","volume":"55","author":"Borrel","year":"2015","journal-title":"J. Chem. Inf. Model."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"W436","DOI":"10.1093\/nar\/gkv462","article-title":"PockDrug-Server: A New Web Server for Predicting Pocket Druggability on Holo and Apo Proteins","volume":"43","author":"Hussein","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Verkhivker, G., Alshahrani, M., and Gupta, G. (2023). Balancing Functional Tradeoffs between Protein Stability and ACE2 Binding in the SARS-CoV-2 Omicron BA.2, BA.2.75 and XBB Lineages: Dynamics-Based Network Models Reveal Epistatic Effects Modulating Compensatory Dynamic and Energetic Changes. Viruses, 15.","DOI":"10.1101\/2023.03.21.533701"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1016\/j.cell.2020.08.012","article-title":"Deep Mutational Scanning of SARS-CoV-2 Receptor Binding Domain Reveals Constraints on Folding and ACE2 Binding","volume":"182","author":"Starr","year":"2020","journal-title":"Cell"},{"key":"ref_133","doi-asserted-by":"crossref","unstructured":"Starr, T.N., Greaney, A.J., Stewart, C.M., Walls, A.C., Hannon, W.W., Veesler, D., and Bloom, J.D. (2022). Deep Mutational Scans for ACE2 Binding, RBD Expression, and Antibody Escape in the SARS-CoV-2 Omicron BA.1 and BA.2 Receptor-Binding Domains. PLoS Pathog., 18.","DOI":"10.1101\/2022.09.20.508745"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1016\/j.chom.2022.09.002","article-title":"Antigenic Characterization of the SARS-CoV-2 Omicron Subvariant BA.2.75","volume":"30","author":"Wang","year":"2022","journal-title":"Cell Host Microbe"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"4405","DOI":"10.1038\/s41467-023-39942-z","article-title":"Structural Basis for Receptor Binding and Broader Interspecies Receptor Recognition of Currently Circulating Omicron Sub-Variants","volume":"14","author":"Zhao","year":"2023","journal-title":"Nat Commun."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"110786","DOI":"10.1016\/j.celrep.2022.110786","article-title":"Inter-Domain Communication in SARS-CoV-2 Spike Proteins Controls Protease-Triggered Cell Entry","volume":"39","author":"Qing","year":"2022","journal-title":"Cell Rep."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1038\/s41423-020-0374-2","article-title":"Fusion Mechanism of 2019-nCoV and Fusion Inhibitors Targeting HR1 Domain in Spike Protein","volume":"17","author":"Xia","year":"2020","journal-title":"Cell. Mol. Immunol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/s41422-020-0305-x","article-title":"Inhibition of SARS-CoV-2 (Previously 2019-nCoV) Infection by a Highly Potent Pan-Coronavirus Fusion Inhibitor Targeting Its Spike Protein That Harbors a High Capacity to Mediate Membrane Fusion","volume":"30","author":"Xia","year":"2020","journal-title":"Cell Res."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1021\/acs.jpcb.0c10637","article-title":"Dynamic Network Modeling of Allosteric Interactions and Communication Pathways in the SARS-CoV-2 Spike Trimer Mutants: Differential Modulation of Conformational Landscapes and Signal Transmission via Cascades of Regulatory Switches","volume":"125","author":"Verkhivker","year":"2021","journal-title":"J. Phys. Chem. B"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"4596","DOI":"10.1021\/acs.jpcb.1c00395","article-title":"Integrated Biophysical Modeling of the SARS-CoV-2 Spike Protein Binding and Allosteric Interactions with Antibodies","volume":"125","author":"Verkhivker","year":"2021","journal-title":"J. Phys. Chem. B"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"4578","DOI":"10.1021\/acs.jctc.1c00372","article-title":"Dynamic Profiling of Binding and Allosteric Propensities of the SARS-CoV-2 Spike Protein with Different Classes of Antibodies: Mutational and Perturbation-Based Scanning Reveals the Allosteric Duality of Functionally Adaptable Hotspots","volume":"17","author":"Verkhivker","year":"2021","journal-title":"J. Chem. Theory Comput."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1021\/acs.biochem.1c00139","article-title":"Comparative Perturbation-Based Modeling of the SARS-CoV-2 Spike Protein Binding with Host Receptor and Neutralizing Antibodies: Structurally Adaptable Allosteric Communication Hotspots Define Spike Sites Targeted by Global Circulating Mutations","volume":"60","author":"Verkhivker","year":"2021","journal-title":"Biochemistry"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/10\/2073\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:04:18Z","timestamp":1760130258000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/10\/2073"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,10]]},"references-count":142,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2023,10]]}},"alternative-id":["v15102073"],"URL":"https:\/\/doi.org\/10.3390\/v15102073","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,10]]}}}