Steered Molecular Dynamics Simulations for Studying Protein–Ligand Interaction in Cyclin-Dependent Kinase 5
Citations Over TimeTop 10% of 2014 papers
Abstract
In this study, we applied steered molecular dynamics (SMD) simulations to investigate the unbinding mechanism of nine inhibitors of the enzyme cyclin-dependent kinase 5 (CDK5). The study had two major objectives: (i) to create a correlation between the unbinding force profiles and the inhibition activities of these compounds expressed as IC50 values; (ii) to investigate the unbinding mechanism and to reveal atomistic insights, which could help identify accessory binding sites and transient interactions. Overall, we carried out 1.35 μs of cumulative SMD simulations. We showed that SMD could qualitatively discriminate binders from nonbinders, while it failed to properly rank series of inhibitors, particularly when IC50 values were too similar. From a mechanistic standpoint, SMD provided useful insights related to transient and dynamical interactions, which could complement static description obtained by X-ray crystallography experiments. In conclusion, the present study represents a further step toward a systematic exploitation of SMD and other dynamical approaches in structure-based drug design and computational medicinal chemistry.
Related Papers
- What Educational Mechanism We Need(2007)
- A Probe into the Development of Community Sports and the Innovation of Its System and Mechanism(2011)
- On the Theory of Social Mechanism(2007)
- A Study on Mechanism of Synergic Development of the Regional High -tech In dustries between Mainland and Taiwan(2002)