A Self-Adaptive Steered Molecular Dynamics Method Based on Minimization of Stretching Force Reveals the Binding Affinity of Protein–Ligand Complexes
Binding affinity prediction of protein–ligand complexes has attracted widespread interest. In this study, a self-adaptive steered molecular dynamics (SMD) method is proposed to reveal the binding affinity of protein–ligand complexes. The SMD method is executed through adjusting pulling direction to...
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MDPI AG
2015-10-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/20/10/19236 |
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doaj-456e913bcfbf4b76b5f907638cda95792020-11-24T22:54:35ZengMDPI AGMolecules1420-30492015-10-012010192361925110.3390/molecules201019236molecules201019236A Self-Adaptive Steered Molecular Dynamics Method Based on Minimization of Stretching Force Reveals the Binding Affinity of Protein–Ligand ComplexesJunfeng Gu0Hongxia Li1Xicheng Wang2State Key Laboratory of Structural Analysis for Industrial Equipment, Department of Engineering Mechanics, Dalian University of Technology, Dalian 116023, ChinaSchool of Mechanical Engineering, Dalian University of Technology, Dalian 116023, ChinaState Key Laboratory of Structural Analysis for Industrial Equipment, Department of Engineering Mechanics, Dalian University of Technology, Dalian 116023, ChinaBinding affinity prediction of protein–ligand complexes has attracted widespread interest. In this study, a self-adaptive steered molecular dynamics (SMD) method is proposed to reveal the binding affinity of protein–ligand complexes. The SMD method is executed through adjusting pulling direction to find an optimum trajectory of ligand dissociation, which is realized by minimizing the stretching force automatically. The SMD method is then used to simulate the dissociations of 19 common protein–ligand complexes which are derived from two homology families, and the binding free energy values are gained through experimental techniques. Results show that the proposed SMD method follows a different dissociation pathway with lower a rupture force and energy barrier when compared with the conventional SMD method, and further analysis indicates the rupture forces of the complexes in the same protein family correlate well with their binding free energy, which reveals the possibility of using the proposed SMD method to identify the active ligand.http://www.mdpi.com/1420-3049/20/10/19236binding affinitysteered molecular dynamicsrupture forceprotein–ligand unbindingoptimization |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Junfeng Gu Hongxia Li Xicheng Wang |
| spellingShingle |
Junfeng Gu Hongxia Li Xicheng Wang A Self-Adaptive Steered Molecular Dynamics Method Based on Minimization of Stretching Force Reveals the Binding Affinity of Protein–Ligand Complexes Molecules binding affinity steered molecular dynamics rupture force protein–ligand unbinding optimization |
| author_facet |
Junfeng Gu Hongxia Li Xicheng Wang |
| author_sort |
Junfeng Gu |
| title |
A Self-Adaptive Steered Molecular Dynamics Method Based on Minimization of Stretching Force Reveals the Binding Affinity of Protein–Ligand Complexes |
| title_short |
A Self-Adaptive Steered Molecular Dynamics Method Based on Minimization of Stretching Force Reveals the Binding Affinity of Protein–Ligand Complexes |
| title_full |
A Self-Adaptive Steered Molecular Dynamics Method Based on Minimization of Stretching Force Reveals the Binding Affinity of Protein–Ligand Complexes |
| title_fullStr |
A Self-Adaptive Steered Molecular Dynamics Method Based on Minimization of Stretching Force Reveals the Binding Affinity of Protein–Ligand Complexes |
| title_full_unstemmed |
A Self-Adaptive Steered Molecular Dynamics Method Based on Minimization of Stretching Force Reveals the Binding Affinity of Protein–Ligand Complexes |
| title_sort |
self-adaptive steered molecular dynamics method based on minimization of stretching force reveals the binding affinity of protein–ligand complexes |
| publisher |
MDPI AG |
| series |
Molecules |
| issn |
1420-3049 |
| publishDate |
2015-10-01 |
| description |
Binding affinity prediction of protein–ligand complexes has attracted widespread interest. In this study, a self-adaptive steered molecular dynamics (SMD) method is proposed to reveal the binding affinity of protein–ligand complexes. The SMD method is executed through adjusting pulling direction to find an optimum trajectory of ligand dissociation, which is realized by minimizing the stretching force automatically. The SMD method is then used to simulate the dissociations of 19 common protein–ligand complexes which are derived from two homology families, and the binding free energy values are gained through experimental techniques. Results show that the proposed SMD method follows a different dissociation pathway with lower a rupture force and energy barrier when compared with the conventional SMD method, and further analysis indicates the rupture forces of the complexes in the same protein family correlate well with their binding free energy, which reveals the possibility of using the proposed SMD method to identify the active ligand. |
| topic |
binding affinity steered molecular dynamics rupture force protein–ligand unbinding optimization |
| url |
http://www.mdpi.com/1420-3049/20/10/19236 |
| work_keys_str_mv |
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