title: Efficient sampling over rough energy landscapes with high barriers: A combination of metadynamics with integrated tempering sampling.
abstract: In order to efficiently overcome high free energy barriers embedded in a complex energy landscape and calculate overall thermodynamics properties using molecular dynamics simulations, we developed and implemented a sampling strategy by combining the metadynamics with (selective) integrated tempering sampling (ITS/SITS) method. The dominant local minima on the potential energy surface (PES) are partially exalted by accumulating history-dependent potentials as in metadynamics, and the sampling over the entire PES is further enhanced by ITS/SITS. With this hybrid method, the simulated system can be rapidly driven across the dominant barrier along selected collective coordinates. Then, ITS/SITS ensures a fast convergence of the sampling over the entire PES and an efficient calculation of the overall thermodynamic properties of the simulation system. To test the accuracy and efficiency of this method, we first benchmarked this method in the calculation of ϕ - ψ distribution of alanine dipeptide in explicit solvent. We further applied it to examine the design of template molecules for aromatic meta-C-H activation in solutions and investigate solution conformations of the nonapeptide Bradykinin involving slow cis-trans isomerizations of three proline residues.
authors.affiliation: Institute of Theoretical and Computational Chemistry, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
authors.forename: Y Isaac
authors.initials: YI
authors.lastname: Yang
authors.affiliation: Institute of Theoretical and Computational Chemistry, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Institute of Theoretical and Computational Chemistry, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Che
authors.affiliation: Institute of Theoretical and Computational Chemistry, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
authors.forename: Lijiang
authors.initials: L
authors.lastname: Yang
authors.affiliation: Institute of Theoretical and Computational Chemistry, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
authors.forename: Yi Qin
authors.initials: YQ
authors.lastname: Gao
mesh_terms: D001920:Bradykinin / Q000737:chemistry; D004151:Dipeptides / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D011804:Quinolines / Q000737:chemistry; D012997:Solvents / Q000737:chemistry
chemical_list: D004151:Dipeptides; D011804:Quinolines; D012997:Solvents; C542964:1,2,3,4-tetrahydroquinoline; D001920:Bradykinin