Enhanced-Sampling Simulations for the Estimation of Ligand Binding Kinetics: Current Status and Perspective
The dissociation rate (koff) associated with ligand unbinding events from proteins is a parameter of fundamental importance in drug design. Here we review recent major advancements in molecular simulation methodologies for the prediction of koff. Next, we discuss the impact of the potential energy f...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2022.899805/full |
| _version_ | 1818205615208529920 |
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| author | Katya Ahmad Andrea Rizzi Andrea Rizzi Riccardo Capelli Davide Mandelli Wenping Lyu Wenping Lyu Paolo Carloni Paolo Carloni |
| author_facet | Katya Ahmad Andrea Rizzi Andrea Rizzi Riccardo Capelli Davide Mandelli Wenping Lyu Wenping Lyu Paolo Carloni Paolo Carloni |
| author_sort | Katya Ahmad |
| collection | DOAJ |
| description | The dissociation rate (koff) associated with ligand unbinding events from proteins is a parameter of fundamental importance in drug design. Here we review recent major advancements in molecular simulation methodologies for the prediction of koff. Next, we discuss the impact of the potential energy function models on the accuracy of calculated koff values. Finally, we provide a perspective from high-performance computing and machine learning which might help improve such predictions. |
| first_indexed | 2024-12-12T03:59:57Z |
| format | Article |
| id | doaj.art-14bf3dc338c247c8bf5b4ef51f803dc3 |
| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-12-12T03:59:57Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-14bf3dc338c247c8bf5b4ef51f803dc32022-12-22T00:39:05ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2022-06-01910.3389/fmolb.2022.899805899805Enhanced-Sampling Simulations for the Estimation of Ligand Binding Kinetics: Current Status and PerspectiveKatya Ahmad0Andrea Rizzi1Andrea Rizzi2Riccardo Capelli3Davide Mandelli4Wenping Lyu5Wenping Lyu6Paolo Carloni7Paolo Carloni8Computational Biomedicine (IAS-5/INM-9), Forschungszentrum Jülich, Jülich, GermanyComputational Biomedicine (IAS-5/INM-9), Forschungszentrum Jülich, Jülich, GermanyAtomistic Simulations, Istituto Italiano di Tecnologia, Genova, ItalyDepartment of Applied Science and Technology (DISAT), Politecnico di Torino, Torino, ItalyComputational Biomedicine (IAS-5/INM-9), Forschungszentrum Jülich, Jülich, GermanyWarshel Institute for Computational Biology, School of Life and Health Sciences, The Chinese University of Hong Kong (Shenzhen), Shenzhen, ChinaSchool of Chemistry and Materials Science, University of Science and Technology of China, Hefei, ChinaComputational Biomedicine (IAS-5/INM-9), Forschungszentrum Jülich, Jülich, GermanyMolecular Neuroscience and Neuroimaging (INM-11), Forschungszentrum Jülich, Jülich, GermanyThe dissociation rate (koff) associated with ligand unbinding events from proteins is a parameter of fundamental importance in drug design. Here we review recent major advancements in molecular simulation methodologies for the prediction of koff. Next, we discuss the impact of the potential energy function models on the accuracy of calculated koff values. Finally, we provide a perspective from high-performance computing and machine learning which might help improve such predictions.https://www.frontiersin.org/articles/10.3389/fmolb.2022.899805/fullkineticsdrug discoveryQM/MMparallel computingmachine learningenhanced sampling |
| spellingShingle | Katya Ahmad Andrea Rizzi Andrea Rizzi Riccardo Capelli Davide Mandelli Wenping Lyu Wenping Lyu Paolo Carloni Paolo Carloni Enhanced-Sampling Simulations for the Estimation of Ligand Binding Kinetics: Current Status and Perspective Frontiers in Molecular Biosciences kinetics drug discovery QM/MM parallel computing machine learning enhanced sampling |
| title | Enhanced-Sampling Simulations for the Estimation of Ligand Binding Kinetics: Current Status and Perspective |
| title_full | Enhanced-Sampling Simulations for the Estimation of Ligand Binding Kinetics: Current Status and Perspective |
| title_fullStr | Enhanced-Sampling Simulations for the Estimation of Ligand Binding Kinetics: Current Status and Perspective |
| title_full_unstemmed | Enhanced-Sampling Simulations for the Estimation of Ligand Binding Kinetics: Current Status and Perspective |
| title_short | Enhanced-Sampling Simulations for the Estimation of Ligand Binding Kinetics: Current Status and Perspective |
| title_sort | enhanced sampling simulations for the estimation of ligand binding kinetics current status and perspective |
| topic | kinetics drug discovery QM/MM parallel computing machine learning enhanced sampling |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2022.899805/full |
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