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| Main Authors: | , |
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| Format: | Preprint |
| Published: |
2026
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| Subjects: | |
| Online Access: | https://arxiv.org/abs/2605.16070 |
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| _version_ | 1866913132783337472 |
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| author | Ocana, Alberto Espinosa, Jorge R. |
| author_facet | Ocana, Alberto Espinosa, Jorge R. |
| contents | Antibody-based therapeutics-including antibody-drug conjugates (ADCs), bispecific antibodies, and novel formats-are reshaping oncology, yet key determinants of efficacy, safety, and manufacturability frequently emerge after conjugation and formulation. We argue that computational biophysics provides an underexploited framework to address this gap by connecting molecular interactions to biological outcomes. We highlight how molecular dynamics, coarse-grained simulations, and free energy calculations reveal how conjugation site, linker chemistry, and drug-antibody ratio reshape conformational landscapes. We emphasize structural coupling between antibody, linker, and payload, with implications for antigen binding, internalization, and developability. We propose that integrating physics-based modeling into development pipelines-alongside experimental validation-can reduce empirical iteration and de-risk translation. As force fields, and hybrid physics-machine-learning methods improve, this field is poised to become a central driver of next-generation ADC design. |
| format | Preprint |
| id |
arxiv_https___arxiv_org_abs_2605_16070 |
| institution | arXiv |
| publishDate | 2026 |
| record_format | arxiv |
| spellingShingle | Biophysical Considerations for Rational Antibody and ADC Design Ocana, Alberto Espinosa, Jorge R. Soft Condensed Matter Biological Physics Antibody-based therapeutics-including antibody-drug conjugates (ADCs), bispecific antibodies, and novel formats-are reshaping oncology, yet key determinants of efficacy, safety, and manufacturability frequently emerge after conjugation and formulation. We argue that computational biophysics provides an underexploited framework to address this gap by connecting molecular interactions to biological outcomes. We highlight how molecular dynamics, coarse-grained simulations, and free energy calculations reveal how conjugation site, linker chemistry, and drug-antibody ratio reshape conformational landscapes. We emphasize structural coupling between antibody, linker, and payload, with implications for antigen binding, internalization, and developability. We propose that integrating physics-based modeling into development pipelines-alongside experimental validation-can reduce empirical iteration and de-risk translation. As force fields, and hybrid physics-machine-learning methods improve, this field is poised to become a central driver of next-generation ADC design. |
| title | Biophysical Considerations for Rational Antibody and ADC Design |
| topic | Soft Condensed Matter Biological Physics |
| url | https://arxiv.org/abs/2605.16070 |