Academic Journal
High-throughput binding affinity calculations at extreme scales
| العنوان: | High-throughput binding affinity calculations at extreme scales |
|---|---|
| المؤلفون: | Dakka, J, Turilli, M, Wright, DW, Zasada, SJ, Balasubramanian, V, Wan, S, Coveney, PV, Jha, S |
| المصدر: | BMC Bioinformatics , 19 (Suppl 18) , Article 482. (2018) |
| سنة النشر: | 2018 |
| المجموعة: | University College London: UCL Discovery |
| الوصف: | BACKGROUND: Resistance to chemotherapy and molecularly targeted therapies is a major factor in limiting the effectiveness of cancer treatment. In many cases, resistance can be linked to genetic changes in target proteins, either pre-existing or evolutionarily selected during treatment. Key to overcoming this challenge is an understanding of the molecular determinants of drug binding. Using multi-stage pipelines of molecular simulations we can gain insights into the binding free energy and the residence time of a ligand, which can inform both stratified and personal treatment regimes and drug development. To support the scalable, adaptive and automated calculation of the binding free energy on high-performance computing resources, we introduce the High-throughput Binding Affinity Calculator (HTBAC). HTBAC uses a building block approach in order to attain both workflow flexibility and performance. RESULTS: We demonstrate close to perfect weak scaling to hundreds of concurrent multi-stage binding affinity calculation pipelines. This permits a rapid time-to-solution that is essentially invariant of the calculation protocol, size of candidate ligands and number of ensemble simulations. CONCLUSIONS: As such, HTBAC advances the state of the art of binding affinity calculations and protocols. HTBAC provides the platform to enable scientists to study a wide range of cancer drugs and candidate ligands in order to support personalized clinical decision making based on genome sequencing and drug discovery. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | text |
| اللغة: | English |
| Relation: | https://discovery.ucl.ac.uk/id/eprint/10064861/1/s12859-018-2506-6.pdf; https://discovery.ucl.ac.uk/id/eprint/10064861/ |
| الاتاحة: | https://discovery.ucl.ac.uk/id/eprint/10064861/1/s12859-018-2506-6.pdf https://discovery.ucl.ac.uk/id/eprint/10064861/ |
| Rights: | open |
| رقم الانضمام: | edsbas.71B113F4 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |