Mapping of antibody epitopes based on docking and homology modeling
Israel T. Desta
Department of Biomedical Engineering, Boston University, Boston, Massachusetts, USA
Contribution: Conceptualization, Methodology, Investigation, Writing - original draft, Writing - review & editing, Validation
Search for more papers by this authorSergei Kotelnikov
Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, New York, USA
Contribution: Conceptualization, Methodology, Investigation, Writing - original draft, Writing - review & editing
Search for more papers by this authorGeorge Jones
Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, New York, USA
Contribution: Methodology, Validation, Investigation
Search for more papers by this authorUsman Ghani
Department of Biomedical Engineering, Boston University, Boston, Massachusetts, USA
Contribution: Methodology, Validation, Investigation
Search for more papers by this authorMikhail Abyzov
Innopolis University, Innopolis, Russia
Contribution: Validation, Methodology, Writing - review & editing
Search for more papers by this authorYaroslav Kholodov
Innopolis University, Innopolis, Russia
Contribution: Investigation, Validation, Writing - review & editing
Search for more papers by this authorDaron M. Standley
Department of Genome Informatics, Osaka University, Osaka, Japan
Center for Infectious Disease Education and Research, Osaka University, Osaka, Japan
Contribution: Investigation, Validation, Writing - review & editing
Search for more papers by this authorMaria Sabitova
Department of Mathematics, CUNY Queens College, Flushing, New York, USA
Contribution: Writing - review & editing, Formal analysis, Writing - original draft
Search for more papers by this authorDmitri Beglov
Department of Biomedical Engineering, Boston University, Boston, Massachusetts, USA
Contribution: Validation, Methodology
Search for more papers by this authorCorresponding Author
Sandor Vajda
Department of Biomedical Engineering, Boston University, Boston, Massachusetts, USA
Correspondence
Sandor Vajda, Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA.
Email: [email protected]
Dima Kozakov, Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY 11794, USA.
Email: [email protected]
Contribution: Writing - review & editing, Writing - original draft, Conceptualization, Investigation, Validation, Methodology
Search for more papers by this authorCorresponding Author
Dima Kozakov
Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, New York, USA
Correspondence
Sandor Vajda, Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA.
Email: [email protected]
Dima Kozakov, Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY 11794, USA.
Email: [email protected]
Contribution: Conceptualization, Writing - original draft, Writing - review & editing, Methodology, Investigation, Validation
Search for more papers by this authorIsrael T. Desta
Department of Biomedical Engineering, Boston University, Boston, Massachusetts, USA
Contribution: Conceptualization, Methodology, Investigation, Writing - original draft, Writing - review & editing, Validation
Search for more papers by this authorSergei Kotelnikov
Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, New York, USA
Contribution: Conceptualization, Methodology, Investigation, Writing - original draft, Writing - review & editing
Search for more papers by this authorGeorge Jones
Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, New York, USA
Contribution: Methodology, Validation, Investigation
Search for more papers by this authorUsman Ghani
Department of Biomedical Engineering, Boston University, Boston, Massachusetts, USA
Contribution: Methodology, Validation, Investigation
Search for more papers by this authorMikhail Abyzov
Innopolis University, Innopolis, Russia
Contribution: Validation, Methodology, Writing - review & editing
Search for more papers by this authorYaroslav Kholodov
Innopolis University, Innopolis, Russia
Contribution: Investigation, Validation, Writing - review & editing
Search for more papers by this authorDaron M. Standley
Department of Genome Informatics, Osaka University, Osaka, Japan
Center for Infectious Disease Education and Research, Osaka University, Osaka, Japan
Contribution: Investigation, Validation, Writing - review & editing
Search for more papers by this authorMaria Sabitova
Department of Mathematics, CUNY Queens College, Flushing, New York, USA
Contribution: Writing - review & editing, Formal analysis, Writing - original draft
Search for more papers by this authorDmitri Beglov
Department of Biomedical Engineering, Boston University, Boston, Massachusetts, USA
Contribution: Validation, Methodology
Search for more papers by this authorCorresponding Author
Sandor Vajda
Department of Biomedical Engineering, Boston University, Boston, Massachusetts, USA
Correspondence
Sandor Vajda, Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA.
Email: [email protected]
Dima Kozakov, Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY 11794, USA.
Email: [email protected]
Contribution: Writing - review & editing, Writing - original draft, Conceptualization, Investigation, Validation, Methodology
Search for more papers by this authorCorresponding Author
Dima Kozakov
Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, New York, USA
Correspondence
Sandor Vajda, Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA.
Email: [email protected]
Dima Kozakov, Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY 11794, USA.
Email: [email protected]
Contribution: Conceptualization, Writing - original draft, Writing - review & editing, Methodology, Investigation, Validation
Search for more papers by this authorIsrael T. Desta and Sergei Kotelnikov Joint first authors.
Funding information: National Institutes of Health; National Science Foundation, Grant/Award Number: DMS 2054251; National Institute of General Medical Sciences, Grant/Award Numbers: R43GM134769, RM1135136, R01 GM140098, R35GM118078
Abstract
Antibodies are key proteins produced by the immune system to target pathogen proteins termed antigens via specific binding to surface regions called epitopes. Given an antigen and the sequence of an antibody the knowledge of the epitope is critical for the discovery and development of antibody based therapeutics. In this work, we present a computational protocol that uses template-based modeling and docking to predict epitope residues. This protocol is implemented in three major steps. First, a template-based modeling approach is used to build the antibody structures. We tested several options, including generation of models using AlphaFold2. Second, each antibody model is docked to the antigen using the fast Fourier transform (FFT) based docking program PIPER. Attention is given to optimally selecting the docking energy parameters depending on the input data. In particular, the van der Waals energy terms are reduced for modeled antibodies relative to x-ray structures. Finally, ranking of antigen surface residues is produced. The ranking relies on the docking results, that is, how often the residue appears in the docking poses' interface, and also on the energy favorability of the docking pose in question. The method, called PIPER-Map, has been tested on a widely used antibody–antigen docking benchmark. The results show that PIPER-Map improves upon the existing epitope prediction methods. An interesting observation is that epitope prediction accuracy starting from antibody sequence alone does not significantly differ from that of starting from unbound (i.e., separately crystallized) antibody structure.
CONFLICT OF INTEREST
The PIPER docking program has been licensed by Boston University to Acpharis Inc. Acpharis, in turn, offers commercial sublicenses of PIPER. Dima Kozakov and Sandor Vajda consult for Acpharis and own stock in the company, Dmitri Beglov is the CEO of the company. However, the ClusPro server, implementing the PIPER program, is freely available to non-commercial use at https://cluspro.bu.edu/.
Open Research
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Supporting Information
| Filename | Description |
|---|---|
| prot26420-sup-0001-supinfo.docxWord 2007 document , 55.4 KB | Appendix S1 Supporting Information |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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