Multi-Scale Free Energy Landscape calculation method by combination of coarse-grained and all-atom models

We propose a new multi-scale molecular dynamics simulation method for calculating free-energy landscapes of biomolecular systems, namely the Multi-Scale Free Energy Landscape calculation method (MSFEL). This method is designed to simultaneously achieve high accuracy and sampling efficiency using a combination of coarse-grained and all-atom models. First, the coarse-grained model is used for calculation of a rough energy landscape over a broad conformational space. Subsequently the all-atom model is used to increase the sampling accuracy of local energy landscapes. MSFEL was applied to Met-enkephalin and Trpzip2, and was demonstrated to be more efficient in conformational sampling compared to conventional molecular dynamics.