Dr. Gennady Verkhivker

Dr. Gennady Verkhivker

Professor
Schmid College of Science and Technology; Computational and Data Science
School of Pharmacy
Office Location: Hashinger Science Center 118
Phone: (714) 516-4586
Website: http://compbiosciences.chapman.edu/
Scholarly Works:
Digital Commons
Education:
Lomonosov Moscow State University, Bachelor of Science
Lomonosov Moscow State University, Master of Science

Biography

Dr. Verkhivker is currently a Professor of Computational Biology. He is also an Adjunct Professor of Pharmacology at the Department of Pharmacology, UC San Diego. His research activities are in the areas of computational cancer biology, translational bioinformatics, and computational pharmacology. He received his PhD in Physical Chemistry from Moscow University and completed a postdoctoral fellowship in computational biophysics from University of Illinois at Chicago. In 2000-2005, Dr. Verkhivker has held various research and management positions at Pfizer Global Research and Development, San Diego.  Since 2002, he has been Adjunct Professor of Pharmacology at the Skaggs School of Pharmacy and Pharmaceutical Sciences, UC San Diego. In 2006, he joined School of Pharmacy and Center for Bioinformatics, The University of Kansas as a Professor of Pharmaceutical Chemistry and Bioinformatics. Dr. Verkhivker returned to California in 2011 and joined Chapman University in August 2011 as a Full Professor of Computational Biology. Upon arrival to Chapman, Dr. Verkhivker has established a dynamic research group engaged in translational research that attracted a large cohort of undergraduate and graduate students.  He has been involved in various global University initiatives and collaborations. Dr. Verkhivker has served on a number of important committees including Search Committee for new Found Dean of BioPharmacy School. He is also chairing the Doctoral Steering Committee of the newly approved PhD Graduate Program in Computational Sciences.

Recent Creative, Scholarly Work and Publications

Agajanian S, Alshahrani M, Bai F, Tao P, Verkhivker GM. Exploring and Learning the Universe of Protein Allostery Using Artificial Intelligence Augmented Biophysical and Computational Approaches. J Chem Inf Model. 2023 Mar 13;63(5):1413-1428. doi: 10.1021/acs.jcim.2c01634. Epub 2023 Feb 24. PMID: 36827465.
Verkhivker G, Alshahrani M, Gupta G. 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. 2023 Apr 2;24(7):6642. doi: 10.3390/ijms24076642. PMID: 37047615; PMCID: PMC10094791.
Verkhivker G, Alshahrani M, Gupta G, Xiao S, Tao P. From Deep Mutational Mapping of Allosteric Protein Landscapes to Deep Learning of Allostery and Hidden Allosteric Sites: Zooming in on "Allosteric Intersection" of Biochemical and Big Data Approaches. Int J Mol Sci. 2023 Apr 24;24(9):7747. doi: 10.3390/ijms24097747. PMID: 37175454; PMCID: PMC10178073.
Verkhivker G, Alshahrani M, Gupta G, Xiao S, Tao P. Probing Conformational Landscapes of Binding and Allostery in the SARS-CoV-2 Omicron Variant Complexes Using Microsecond Atomistic Simulations and Perturbation-Based Profiling Approaches: Hidden Role of Omicron Mutations as Modulators of Allosteric Signaling and Epistatic Relationships. bioRxiv [Preprint]. 2023 May 4:2023.05.03.539337. doi: 10.1101/2023.05.03.539337. PMID: 37205479; PMCID: PMC10187228.
Ibrahim MT, Verkhivker GM, Misra J, Tao P. Novel Allosteric Effectors Targeting Human Transcription Factor TEAD. Int J Mol Sci. 2023 May 19;24(10):9009. doi: 10.3390/ijms24109009. PMID: 37240355; PMCID: PMC10219411.
Verkhivker G, Alshahrani M, Gupta G. 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. 2023 May 10;15(5):1143. doi: 10.3390/v15051143. PMID: 37243229; PMCID: PMC10221141.
Xiao S, Alshahrani M, Gupta G, Tao P, Verkhivker G. Markov State Models and Perturbation-Based Approaches Reveal Distinct Dynamic Signatures and Hidden Allosteric Pockets in the Emerging SARS-Cov-2 Spike Omicron Variants Complexes with the Host Receptor: The Interplay of Dynamics and Convergent Evolution Modulates Allostery and Functional Mechanisms. bioRxiv [Preprint]. 2023 May 22:2023.05.20.541592. doi: 10.1101/2023.05.20.541592. PMID: 37292827; PMCID: PMC10245745.
Verkhivker G, Alshahrani M, Gupta G, Xiao S, Tao P. Probing conformational landscapes of binding and allostery in the SARS-CoV-2 omicron variant complexes using microsecond atomistic simulations and perturbation-based profiling approaches: hidden role of omicron mutations as modulators of allosteric signaling and epistatic relationships. Phys Chem Chem Phys. 2023 Aug 16;25(32):21245-21266. doi: 10.1039/d3cp02042h. PMID: 37548589; PMCID: PMC10536792.
Xiao S, Alshahrani M, Gupta G, Tao P, Verkhivker G. Markov State Models and Perturbation-Based Approaches Reveal Distinct Dynamic Signatures and Hidden Allosteric Pockets in the Emerging SARS-Cov-2 Spike Omicron Variant Complexes with the Host Receptor: The Interplay of Dynamics and Convergent Evolution Modulates Allostery and Functional Mechanisms. J Chem Inf Model. 2023 Aug 28;63(16):5272-5296. doi: 10.1021/acs.jcim.3c00778. Epub 2023 Aug 7. PMID: 37549201.
Alshahrani M, Gupta G, Xiao S, Tao P, Verkhivker G. Examining Functional Linkages Between Conformational Dynamics, Protein Stability and Evolution of Cryptic Binding Pockets in the SARS-CoV-2 Omicron Spike Complexes with the ACE2 Host Receptor: Recombinant Omicron Variants Mediate Variability of Conserved Allosteric Sites and Binding Epitopes. bioRxiv [Preprint]. 2023 Sep 12:2023.09.11.557205. doi: 10.1101/2023.09.11.557205. PMID: 37745525; PMCID: PMC10515794.
Verkhivker G, Alshahrani M, Gupta G. Exploring Conformational Landscapes and Cryptic Binding Pockets in Distinct Functional States of the SARS-CoV-2 Omicron BA.1 and BA.2 Trimers: Mutation-Induced Modulation of Protein Dynamics and Network-Guided Prediction of Variant-Specific Allosteric Binding Sites. Viruses. 2023 Sep 27;15(10):2009. doi: 10.3390/v15102009. PMID: 37896786; PMCID: PMC10610873.
Alshahrani M, Gupta G, Xiao S, Tao P, Verkhivker G. 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. Viruses. 2023 Oct 10;15(10):2073. doi: 10.3390/v15102073. PMID: 37896850; PMCID: PMC10612107.
Raisinghani N, Alshahrani M, Gupta G, Xiao S, Tao P, Verkhivker G. Accurate Characterization of Conformational Ensembles and Binding Mechanisms of the SARS-CoV-2 Omicron BA.2 and BA.2.86 Spike Protein with the Host Receptor and Distinct Classes of Antibodies Using AlphaFold2-Augmented Integrative Computational Modeling. bioRxiv [Preprint]. 2023 Nov 21:2023.11.18.567697. doi: 10.1101/2023.11.18.567697. PMID: 38045395; PMCID: PMC10690158.
Raisinghani N, Alshahrani M, Gupta G, Xiao S, Tao P, Verkhivker G. AlphaFold2-Enabled Atomistic Modeling of Structure, Conformational Ensembles and Binding Energetics of the SARS-CoV-2 Omicron BA.2.86 Spike Protein with ACE2 Host Receptor and Antibodies: Compensatory Functional Effects of Binding Hotspots in Modulating Mechanisms of Receptor Binding and Immune Escape. J. Chem Inf Model. 2023 accepted, in press
Raisinghani N, Alshahrani M, Gupta G, Xiao S, Tao P, Verkhivker G. AlphaFold2-Enabled Atomistic Modeling of Epistatic Binding Mechanisms for the SARS-CoV-2 Spike Omicron XBB.1.5, EG.5 and FLip Variants: Convergent Evolution Hotspots Cooperate to Control Stability and Conformational Adaptability in Balancing ACE2 Binding and Antibody Resistance. bioRxiv [Preprint]. 2023 Dec 12:2023.12.11.571185. doi: 10.1101/2023.12.11.571185. PMID: 38168257; PMCID: PMC10760024.
Xiao S, Ibrahim MT, Verkhivker GM, Zoltowski BD, Tao P. Microsecond Molecular Dynamics Simulations and Markov State Models of Mutation-Induced Allosteric Mechanisms for the Light-Oxygen-Voltage 2 Protein : Revealing Structural Basis of Signal Transmission Induced by Photoactivation of the Light Protein State. bioRxiv [Preprint]. 2023 Dec 23:2023.12.22.573121. doi: 10.1101/2023.12.22.573121. PMID: 38187662; PMCID: PMC10769362.
Xiao S, Ibrahim MT, Verkhivker GM, Zoltowski BD, Tao P. ß-sheets mediate the conformational change and allosteric signal transmission between the As LOV2 termini. J. Comput. Chem. 2023, accepted, in press
Verkhivker G. Conformational Flexibility and Local Frustration in the Functional States of the SARS-CoV-2 Spike B.1.1.7 and B.1.351 Variants: Mutation-Induced Allosteric Modulation Mechanism of Functional Dynamics and Protein Stability. Int J Mol Sci. 2022 Jan 31;23(3):1646. doi: 10.3390/ijms23031646. PMID: 35163572; PMCID: PMC8836237.
Verkhivker GM, Agajanian S, Oztas D, Gupta G. Computational analysis of protein stability and allosteric interaction networks in distinct conformational forms of the SARS-CoV-2 spike D614G mutant: reconciling functional mechanisms through allosteric model of spike regulation. J Biomol Struct Dyn. 2022;40(20):9724-9741. doi: 10.1080/07391102.2021.1933594. Epub 2021 Jun 1. PMID: 34060425
Verkhivker G. Allosteric Determinants of the SARS-CoV-2 Spike Protein Binding with Nanobodies: Examining Mechanisms of Mutational Escape and Sensitivity of the Omicron Variant. Int J Mol Sci. 2022 Feb 16;23(4):2172. doi: 10.3390/ijms23042172. PMID: 35216287; PMCID: PMC8877688
Verkhivker G. Structural and Computational Studies of the SARS-CoV-2 Spike Protein Binding Mechanisms with Nanobodies: From Structure and Dynamics to Avidity-Driven Nanobody Engineering. Int J Mol Sci. 2022 Mar 8;23(6):2928. doi: 10.3390/ijms23062928. PMID: 35328351; PMCID: PMC8951411.
Xiao F, Zhou Z, Song X, Gan M, Long J, Verkhivker G, Hu G. Dissecting mutational allosteric effects in alkaline phosphatases associated with different Hypophosphatasia phenotypes: An integrative computational investigation. PLoS Comput Biol. 2022 Mar 23;18(3):e1010009. doi: 10.1371/journal.pcbi.1010009. PMID: 35320273; PMCID: PMC8979438.
Verkhivker G, Agajanian S, Kassab R, Krishnan K. Computer Simulations and Network-Based Profiling of Binding and Allosteric Interactions of SARS-CoV-2 Spike Variant Complexes and the Host Receptor: Dissecting the Mechanistic Effects of the Delta and Omicron Mutations. Int J Mol Sci. 2022 Apr 15;23(8):4376. doi: 10.3390/ijms23084376. PMID: 35457196; PMCID: PMC9032413.
Verkhivker GM, Agajanian S, Kassab R, Krishnan K. Landscape-Based Protein Stability Analysis and Network Modeling of Multiple Conformational States of the SARS-CoV-2 Spike D614G Mutant: Conformational Plasticity and Frustration-Induced Allostery as Energetic Drivers of Highly Transmissible Spike Variants. J Chem Inf Model. 2022 Apr 25;62(8):1956-1978. doi: 10.1021/acs.jcim.2c00124. Epub 2022 Apr 4. PMID: 35377633
Gennady M. Verkhivker, Steve Agajanian, Deniz Yazar Oztas, Grace Gupta Dynamic Profiling of Binding and Allosteric Propensities of the SARS-CoV-2 Spike Protein with Different Classes of Antibodies: Mutational and Perturbation-Based Scanning Reveal Allosteric Duality of Functionally Adaptable Hotspots bioRxiv 2021.04.13.439743; doi: https://doi.org/10.1101/2021.04.13.439743
Gennady Verkhivker, Steve Agajanian, Ryan Kassab, Keerthi Krishnan Integrating Conformational Dynamics and Perturbation-Based Network Modeling for Mutational Profiling of Binding and Allostery in the SARS-CoV-2 Spike Variant Complexes with Antibodies: Balancing Local and Global Determinants of Mutational Escape Mechanisms bioRxiv 2022.06.17.496646; doi: https://doi.org/10.1101/2022.06.17.496646
Gennady M. Verkhivker, Steve Agajanian, Ryan Kassab, Keerthi Krishnan Hierarchical Computational Modeling and Dynamic Network Analysis of Allosteric Regulation in the SARS-CoV-2 Spike Omicron Trimer Structures: Omicron Mutations Cooperate to Allosterically Control Balance of Protein Stability and Conformational Adaptability. bioRxiv 2022.04.11.487920; doi: https://doi.org/10.1101/2022.04.11.487920
Gennady Verkhivker, Steve Agajanian, Ryan Kassab, Keerthi Krishnan. Atomistic Simulations and Network-Based Energetic Profiling of Binding and Allostery in the SARS-CoV-2 Spike Omicron BA.1, BA.1.1, BA.2 and BA.3 Subvariant Complexes with the Host Receptor: Revealing Hidden Functional Roles of the Binding Hotspots in Mediating Epistatic Effects and Long-Range Communication with Allosteric Pockets. bioRxiv 2022.09.05.506698; doi: https://doi.org/10.1101/2022.09.05.506698
Keerthi Krishnan, Hao Tian, Peng Tao, Gennady M. Verkhivker. Probing Conformational Landscapes and Mechanisms of Allosteric Communication in the Functional States of the ABL Kinase Domain Using Multiscale Simulations and Network-Based Mutational Profiling of Allosteric Residue Potentials bioRxiv 2022.11.29.518410; doi: https://doi.org/10.1101/2022.11.29.518410
Gennady M. Verkhivker. Conformational Dynamics and Mechanisms of Client Protein Integration into the Hsp90 Chaperone Controlled by Allosteric Interactions of Regulatory Switches: Perturbation-Based Network Approach for Mutational Profiling of the Hsp90 Binding and Allostery. bioRxiv 2022.05.20.492854; doi: https://doi.org/10.1101/2022.05.20.492854
Hadi-Alijanvand H, Di Paola L, Hu G, Leitner DM, Verkhivker GM, Sun P, Poudel H, Giuliani A. Biophysical Insight into the SARS-CoV2 Spike-ACE2 Interaction and Its Modulation by Hepcidin through a Multifaceted Computational Approach. ACS Omega. 2022 May 10;7(20):17024-17042. doi: 10.1021/acsomega.2c00154. PMID: 35600142; PMCID: PMC9113007.
Verkhivker G, Agajanian S, Kassab R, Krishnan K. Integrating Conformational Dynamics and Perturbation-Based Network Modeling for Mutational Profiling of Binding and Allostery in the SARS-CoV-2 Spike Variant Complexes with Antibodies: Balancing Local and Global Determinants of Mutational Escape Mechanisms. Biomolecules. 2022 Jul 10;12(7):964. doi: 10.3390/biom12070964. PMID: 35883520; PMCID: PMC9313167
Verkhivker GM. Conformational Dynamics and Mechanisms of Client Protein Integration into the Hsp90 Chaperone Controlled by Allosteric Interactions of Regulatory Switches: Perturbation-Based Network Approach for Mutational Profiling of the Hsp90 Binding and Allostery. J Phys Chem B. 2022 Jul 19. doi: 10.1021/acs.jpcb.2c03464. Epub ahead of print. PMID: 35853093.
Verkhivker GM, Agajanian S, Kassab R, Krishnan K. Frustration-driven allosteric regulation and signal transmission in the SARS-CoV-2 spike omicron trimer structures: a crosstalk of the omicron mutation sites allosterically regulates tradeoffs of protein stability and conformational adaptability. Phys Chem Chem Phys. 2022 Jul 27;24(29):17723-17743. doi: 10.1039/d2cp01893d. PMID: 35839100
Verkhivker GM. Exploring Mechanisms of Allosteric Regulation and Communication Switching in the Multiprotein Regulatory Complexes of the Hsp90 Chaperone with Cochaperones and Client Proteins: Atomistic Insights from Integrative Biophysical Modeling and Network Analysis of Conformational Landscapes. J Mol Biol. 2022 Sep 15;434(17):167506. doi: 10.1016/j.jmb.2022.167506. Epub 2022 Feb 21. PMID: 35202628
Krishnan K, Kassab R, Agajanian S, Verkhivker G. Interpretable Machine Learning Models for Molecular Design of Tyrosine Kinase Inhibitors Using Variational Autoencoders and Perturbation-Based Approach of Chemical Space Exploration. Int J Mol Sci. 2022 Sep 24;23(19):11262. doi: 10.3390/ijms231911262. PMID: 36232566; PMCID: PMC9569663
Verkhivker G, Agajanian S, Kassab R, Krishnan K. 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. 2022 Sep 29;23(19):11542. doi: 10.3390/ijms231911542. PMID: 36232845; PMCID: PMC9569682
Xiao S, Verkhivker GM, Tao P. Machine learning and protein allostery. Trends Biochem Sci. 2022 Dec 21:S0968-0004(22)00311-5. doi: 10.1016/j.tibs.2022.12.001. Epub ahead of print. PMID: 36564251.
Krishnan K, Tian H, Tao P, Verkhivker GM. Probing conformational landscapes and mechanisms of allosteric communication in the functional states of the ABL kinase domain using multiscale simulations and network-based mutational profiling of allosteric residue potentials. J Chem Phys. 2022 Dec 28;157(24):245101. doi: 10.1063/5.0133826. PMID: 36586979.
Verkhivker GM, Di Paola L. 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. J Phys Chem B. 2021 Jan 28;125(3):850-873. doi: 10.1021/acs.jpcb.0c10637. Epub 2021 Jan 15. PMID: 33448856; PMCID: PMC7839160.
Verkhivker GM, Agajanian S, Oztas DY, Gupta G. 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. Biochemistry. 2021 May 18;60(19):1459-1484. doi: 10.1021/acs.biochem.1c00139. Epub 2021 Apr 26. PMID: 33900725; PMCID: PMC8098775.
Verkhivker GM, Di Paola L. Integrated Biophysical Modeling of the SARS-CoV-2 Spike Protein Binding and Allosteric Interactions with Antibodies. J Phys Chem B. 2021 May 13;125(18):4596-4619. doi: 10.1021/acs.jpcb.1c00395. Epub 2021 Apr 30. PMID: 33929853; PMCID: PMC8098774.
Verkhivker GM, Agajanian S, Oztas D, Gupta G. Computational analysis of protein stability and allosteric interaction networks in distinct conformational forms of the SARS-CoV-2 spike D614G mutant: reconciling functional mechanisms through allosteric model of spike regulation. J Biomol Struct Dyn. 2021 Jun 1:1-18. doi: 10.1080/07391102.2021.1933594. Epub ahead of print. PMID: 34060425.
Computational Analysis of Protein Stability and Allosteric Interaction Networks in Distinct Conformational Forms of the SARS-CoV-2 Spike D614G Mutant: Reconciling Functional Mechanisms through Allosteric Model of Spike Regulation Gennady M. Verkhivker, Steve Agajanian, Denis Oztas, Grace Gupta bioRxiv 2021.01.26.428331; doi: https://doi.org/10.1101/2021.01.26.428331
Verkhivker G, Agajanian S, Oztas D, Gupta G. 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. J Chem Theory Comput. 2021 Jul 13;17(7):4578-4598. doi: 10.1021/acs.jctc.1c00372. Epub 2021 Jun 17. PMID: 34138559.
Dynamic Profiling of Binding and Allosteric Propensities of the SARS-CoV-2 Spike Protein with Different Classes of Antibodies: Mutational and Perturbation-Based Scanning Reveal Allosteric Duality of Functionally Adaptable Hotspots Gennady M. Verkhivker, Steve Agajanian, Deniz Yazar Oztas, Grace Gupta bioRxiv 2021.04.13.439743; doi: https://doi.org/10.1101/2021.04.13.439743
Verkhivker GM, Agajanian S, Oztas DY, Gupta G. Landscape-Based Mutational Sensitivity Cartography and Network Community Analysis of the SARS-CoV-2 Spike Protein Structures: Quantifying Functional Effects of the Circulating D614G Variant. ACS Omega. 2021 Jun 9;6(24):16216-16233. doi: 10.1021/acsomega.1c02336. PMID: 34179666; PMCID: PMC8223427.
Landscape-Based Mutational Sensitivity Cartography and Network Community Analysis of the SARS-CoV-2 Spike Protein Structures: Quantifying Functional Effects of the Circulating Variants Gennady M. Verkhivker, Steve Agajanian, Deniz Yazar Oztas, Grace Gupta bioRxiv 2021.05.18.444742; doi: https://doi.org/10.1101/2021.05.18.444742
Verkhivker, G.; Agajanian, S.; Oztas, D.Y.; Gupta, G. Dissecting Molecular Determinants of Mutational Escape Mechanisms in the SARS-CoV-2 Spike Protein Complexes with Nanobodies: Atomistic Simulations and Ensemble-Based Deep Mutational Scanning of Protein Stability and Binding Interactions. Preprints 2021, 2021070295 (doi: 10.20944/preprints202107.0295.v1).
Verkhivker GM. Making the invisible visible: Toward structural characterization of allosteric states, interaction networks, and allosteric regulatory mechanisms in protein kinases. Curr Opin Struct Biol. 2021 Jul 5;71:71-78. doi: 10.1016/j.sbi.2021.06.002. Epub ahead of print. PMID: 34237520.
Trozzi F, Wang F, Verkhivker G, Zoltowski BD, Tao P. Dimeric allostery mechanism of the plant circadian clock photoreceptor ZEITLUPE. PLoS Comput Biol. 2021 Jul 26;17(7):e1009168. doi: 10.1371/journal.pcbi.1009168. PMID: 34310591; PMCID: PMC8341706.
Deep Mutational Scanning of Dynamic Interaction Networks in the SARS-CoV-2 Spike Protein Complexes: Allosteric Hotspots Control Functional Mimicry and Resilience to Mutational Escape Gennady M. Verkhivker bioRxiv 2021.06.15.448568; doi: https://doi.org/10.1101/2021.06.15.448568
Atomistic Simulations and Deep Mutational Scanning of Protein Stability and Binding Interactions in the SARS-CoV-2 Spike Protein Complexes with Nanobodies: Molecular Determinants of Mutational Escape Mechanisms Gennady M. Verkhivker, Steve Agajanian, Deniz Yasar Oztas, Grace Gupta bioRxiv 2021.07.07.451538; doi: https://doi.org/10.1101/2021.07.07.451538
Verkhivker GM, Agajanian S, Oztas DY, Gupta G. Atomistic Simulations and In Silico Mutational Profiling of Protein Stability and Binding in the SARS-CoV-2 Spike Protein Complexes with Nanobodies: Molecular Determinants of Mutational Escape Mechanisms, ACS Omega. 2021 Sep 27;6(40):26354-26371. doi: 10.1021/acsomega.1c03558. PMID: 34660995; PMCID: PMC8515575
Verkhivker GM, Agajanian S, Oztas DY, Gupta G. Allosteric Control of Structural Mimicry and Mutational Escape in the SARS-CoV-2 Spike Protein Complexes with the ACE2 Decoys and Miniprotein Inhibitors: A Network-Based Approach for Mutational Profiling of Binding and Signaling. J Chem Inf Model. 2021 Oct 25;61(10):5172-5191. doi: 10.1021/acs.jcim.1c00766. Epub 2021 Sep 22. PMID: 34551245.
Verkhivker GM. Making the invisible visible: Toward structural characterization of allosteric states, interaction networks, and allosteric regulatory mechanisms in protein kinases. Curr Opin Struct Biol. 2021 Dec;71:71-78. doi: 10.1016/j.sbi.2021.06.002. Epub 2021 Jul 5. PMID: 34237520.
Verkhivker G. Computational Modeling and Engineering of Allosteric Regulatory Mechanisms in Signaling Proteins: Integration of Multiscale Simulations, Network Biology and Machine Learning. Biophysical journal. 2020 February; 118(3):206A. doi: https://doi.org/10.1016/j.bpj.2019.11.1238.
Verkhivker GM. Molecular Simulations and Network Modeling Reveal an Allosteric Signaling in the SARS-CoV-2 Spike Proteins. J Proteome Res. 2020 Nov 6;19(11):4587-4608. doi: 10.1021/acs.jproteome.0c00654. Epub 2020 Oct 2. PMID: 33006900; PMCID: PMC7640983.
Astl L, Stetz G, Verkhivker GM. Dissecting Molecular Principles of the Hsp90 Chaperone Regulation by Allosteric Modulators Using a Hierarchical Simulation Approach and Network Modeling of Allosteric Interactions: Conformational Selection Dictates the Diversity of Protein Responses and Ligand-Specific Functional Mechanisms. J Chem Theory Comput. 2020 Oct 13;16(10):6656-6677. doi: 10.1021/acs.jctc.0c00503. Epub 2020 Sep 28. PMID: 32941034.
Astl L, Verkhivker GM. Dynamic View of Allosteric Regulation in the Hsp70 Chaperones by J-Domain Cochaperone and Post-Translational Modifications: Computational Analysis of Hsp70 Mechanisms by Exploring Conformational Landscapes and Residue Interaction Networks. J Chem Inf Model. 2020 Mar 23;60(3):1614-1631. doi: 10.1021/acs.jcim.9b01045. Epub 2020 Jan 21. PMID: 31935082.
Sheik Amamuddy O, Veldman W, Manyumwa C, Khairallah A, Agajanian S, Oluyemi O, Verkhivker G, Tastan Bishop O. Integrated Computational Approaches and Tools forAllosteric Drug Discovery. Int J Mol Sci. 2020 Jan 28;21(3):847. doi: 10.3390/ijms21030847. PMID: 32013012; PMCID: PMC7036869.
Stetz G, Astl L, Verkhivker GM. Exploring Mechanisms of Communication Switching in the Hsp90-Cdc37 Regulatory Complexes with Client Kinases through Allosteric Coupling of Phosphorylation Sites: Perturbation-Based Modeling and Hierarchical Community Analysis of Residue Interaction Networks. J Chem Theory Comput. 2020 Jul 14;16(7):4706-4725. doi: 10.1021/acs.jctc.0c00280. Epub 2020 Jun 14. PMID: 32492340.
Astl L, Stetz G, Verkhivker GM. Allosteric Mechanism of the Hsp90 Chaperone Interactions with Cochaperones and Client Proteins by Modulating Communication Spines of Coupled Regulatory Switches: Integrative Atomistic Modeling of Hsp90 Signaling in Dynamic Interaction Networks. J Chem Inf Model. 2020 Jul 27;60(7):3616-3631. doi: 10.1021/acs.jcim.0c00380. Epub 2020 Jun 18. PMID: 32519853.
Xiao F, Song X, Tian P, Gan M, Verkhivker GM, Hu G. Comparative Dynamics and Functional Mechanisms of the CYP17A1 Tunnels Regulated by Ligand Binding. J Chem Inf Model. 2020 Jul 27;60(7):3632-3647. doi: 10.1021/acs.jcim.0c00447. Epub 2020 Jun 22. PMID: 32530640.
Verkhivker GM, Agajanian S, Hu G, Tao P. Allosteric Regulation at the Crossroads of New Technologies: Multiscale Modeling, Networks, and Machine Learning. Front Mol Biosci. 2020 Jul 9;7:136. doi: 10.3389/fmolb.2020.00136. PMID: 32733918; PMCID: PMC7363947.
Sheik Amamuddy O, Verkhivker GM, Tastan Bishop Ö. Impact of Early Pandemic Stage Mutations on Molecular Dynamics of SARS-CoV-2 Mpro. J Chem Inf Model. 2020 Oct 26;60(10):5080-5102. doi: 10.1021/acs.jcim.0c00634. Epub 2020 Sep 16. PMID: 32853525; PMCID: PMC7496595.
Astl L, Stetz G, Verkhivker GM. Allosteric Mechanism of the Hsp90 Chaperone Interactions with Cochaperones and Client Proteins by Modulating Communication Spines of Coupled Regulatory Switches: Integrative Atomistic Modeling of Hsp90 Signaling in Dynamic Interaction Networks. J Chem Inf Model. 2020 Jul 27;60(7):3616-3631. doi: 10.1021/acs.jcim.0c00380. Epub 2020 Jun 18. PMID: 32519853.
Verkhivker G. Coevolution, Dynamics and Allostery Conspire in Shaping Cooperative Binding and Signal Transmission of the SARS-CoV-2 Spike Protein with Human Angiotensin-Converting Enzyme 2. Int J Mol Sci. 2020 Nov 4;21(21):8268. doi: 10.3390/ijms21218268. PMID: 33158276; PMCID: PMC7672574.
Astl L, Tse A, Verkhivker GM. Interrogating Regulatory Mechanisms in Signaling Proteins by Allosteric Inhibitors and Activators: A Dynamic View Through the Lens of Residue Interaction Networks. Adv Exp Med Biol. 2019;1163:187-223. doi: 10.1007/978-981-13-8719-7_9. PMID: 31707705.
Interrogating Regulatory Mechanisms in Signaling Proteins by Allosteric Inhibitors and Activators: A Dynamic View through the Lens of Residue Interaction Networks. Gennady M. Verkhivker, Lindy Astl, Amanda Tse. In Advances in Experimental Medicine and Biology Series. Protein Allostery in Drug Discovery, Springer-Nature, Eds. Jian Zhang and Ruth Nussinov, volume 1163, Series ISSN 0065-2598 DOI 10.1007/978-981-13-8719-7
Integration of Random Forest Classifiers and Deep Convolutional Neural Networks for Classification and Biomolecular Modeling of Cancer Driver Mutations. Agajanian S, Oluyemi O, Verkhivker GM. Front Mol Biosci. 2019 Jun 11;6:44. doi: 10.3389/fmolb.2019.00044. eCollection 2019. PMID: 31245384
Integration of network models and evolutionary analysis into high-throughput modeling of protein dynamics and allosteric regulation: theory, tools and applications. Liang Z, Verkhivker GM, Hu G. Brief Bioinform. 2019 Mar 21. pii: bbz029. doi: 10.1093/bib/bbz029. [Epub ahead of print] PMID: 30911759
Atomistic Modeling of the ABL Kinase Regulation by Allosteric Modulators Using Structural Perturbation Analysis and Community-Based Network Reconstruction of Allosteric Communications. Astl L, Verkhivker GM. J Chem Theory Comput. 2019 May 14;15(5):3362-3380. doi: 10.1021/acs.jctc.9b00119. Epub 2019 May 2. PMID: 31017783
Generative Machine Learning Models for Discovery of selective chemical probes to interrogate protein kinase mechanisms. Agajanian S, Oluyemi O, Verkhivker GM. Nature Communications, Submitted 2019
Amusengeri A, Astl L, Lobb K, Verkhivker GM, Tastan Bishop Ö. Establishing Computational Approaches Towards Identifying Malarial Allosteric Modulators: A Case Study of Plasmodium falciparum Hsp70s. Int J Mol Sci. 2019 Nov 8;20(22):5574. doi: 10.3390/ijms20225574. PMID: 31717270; PMCID: PMC6887781.
Allosteric mechanism of the circadian protein Vivid resolved through Markov state model and machine learning analysis. Zhou H, Dong Z, Verkhivker G, Zoltowski BD, Tao P. PLoS Comput Biol. 2019 Feb 19;15(2):e1006801. doi: 10.1371/journal.pcbi.1006801. eCollection 2019 Feb. PMID: 30779735
Biophysical simulations and structure-based modeling of residue interaction networks in the tumor suppressor proteins reveal functional role of cancer mutation hotspots in molecular communication. Verkhivker GM. Biochim Biophys Acta Gen Subj. 2019 Jan;1863(1):210-225. doi: 10.1016/j.bbagen.2018.10.009. Epub 2018 Oct 16. PMID: 30339916
Data-driven computational analysis of allosteric proteins by exploring protein dynamics, residue coevolution and residue interaction networks. Astl L, Verkhivker GM. Biochim Biophys Acta Gen Subj. 2019 Jul 19. pii: S0304-4165(19)30179-5. doi: 10.1016/j.bbagen.2019.07.008. [Epub ahead of print] PMID: 31330173
Editorial: Machine Learning in Biomolecular Simulations, Gennady Verkhivker, Vojtech Spiwok, Francesco Gervasio Front. Mol. Biosci., 29 August 2019 | https://doi.org/10.3389/fmolb.2019.00076
Computational Modeling of the Hsp90 Interactions with Cochaperones and Small-Molecule Inhibitors. Verkhivker GM. Methods in Molecular Biology,Chaperones : Methods and Protocols. Editors: Calderwood, Stuart K., Prince, Thomas L. (Eds.) 2018;1709:253-273. doi: 10.1007/978-1-4939-7477-1_19.
Dissecting Structure-Encoded Determinants of Allosteric Cross-Talk between Post-Translational Modification Sites in the Hsp90 Chaperones. Stetz G, Tse A, Verkhivker GM. Sci Rep. 2018 May 2;8(1):6899. doi: 10.1038/s41598-018-25329-4.
Dynamics-based community analysis and perturbation response scanning of allosteric interaction networks in the TRAP1 chaperone structures dissect molecular linkage between conformational asymmetry and sequential ATP hydrolysis. Verkhivker GM. Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics 2018 Aug;1866(8):899-912. doi: 10.1016/j.bbapap.2018.04.008. Epub 2018 Apr 21.
Machine Learning Classification and Structure-Functional Analysis of Cancer Mutations Reveal Unique Dynamic and Network Signatures of Driver Sites in Oncogenes and Tumor Suppressor Genes. Agajanian S, Odeyemi O, Bischoff N, Ratra S, Verkhivker GM. J Chem Inf Model. 2018 Oct 22;58(10):2131-2150. doi: 10.1021/acs.jcim.8b00414. Epub 2018 Oct 3. PMID: 30253099
Functional Role and Hierarchy of the Intermolecular Interactions in Binding of Protein Kinase Clients to the Hsp90-Cdc37 Chaperone: Structure-Based Network Modeling of Allosteric Regulation. Stetz G, Verkhivker GM. J Chem Inf Model. 2018 Feb 26;58(2):405-421. doi: 10.1021/acs.jcim.7b00638. Epub 2018 Feb 15.
Design, Synthesis, and Evaluation of Dasatinib-Amino Acid and Dasatinib-Fatty Acid Conjugates as Protein Tyrosine Kinase Inhibitors. Tiwari RK, Brown A, Sadeghiani N, Shirazi AN, Bolton J, Tse A, Verkhivker G, Parang K, Sun G. ChemMedChem. 2017 Jan 5;12(1):86-99. doi: 10.1002/cmdc.201600387. Epub 2016 Dec 5. PMID: 27875633
Computational Analysis of Residue Interaction Networks and Coevolutionary Relationships in the Hsp70 Chaperones: A Community-Hopping Model of Allosteric Regulation and Communication. Stetz G, Verkhivker GM. PLoS Comput Biol. 2017 Jan 17;13(1):e1005299. doi: 10.1371/journal.pcbi.1005299. eCollection 2017 Jan. PMID: 28095400
Network-based modelling and percolation analysis of conformational dynamics and activation in the CDK2 and CDK4 proteins: Dynamic and energetic polarization of the kinase lobes may determine divergence of the regulatory mechanisms. GM Verkhivker. Mol Biosyst. 2017 Oct 24;13(11):2235-2253
Atomistic simulations and network-based modeling of the Hsp90-Cdc37 chaperone binding with Cdk4 client protein: A mechanism of chaperoning kinase clients by exploiting weak spots of intrinsically dynamic kinase domains. Czemeres J, Buse K, Verkhivker GM. PLoS One. 2017 Dec 21;12(12):e0190267. doi: 10.1371/journal.pone.0190267. eCollection 2017
Ensemble-Based Modeling and Rigidity Decomposition of Allosteric Interaction Networks and Communication Pathways in Cyclin-Dependent Kinases: Differentiating Kinase Clients of the Hsp90-Cdc37 Chaperone. Gabrielle Stetz, Amanda Tse, G M. Verkhivker PLoS One. 2017 Nov 2;12(11):e0186089. doi: 10.1371/journal.pone.0186089. eCollection 2017.

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