Free energy reaction root mapping of alanine tripeptide in water

ABSTRACT

We have investigated the free energy surface of alanine tripeptide in water. To elucidate the secondary structure of the amide chain, information on the free energy surface with explicit water at room temperature, and the multidimensional reaction coordinates are required. We studied the minimum free energy paths (MFEPs) connecting reactants, transition structures (TS) and products. To solve this problem, we used the free energy reaction root mapping (FERRMap) method. This is an automated search method to find MFEPs by using umbrella integration and the scaled hypersphere search method. We calculated the four-dimensional free energy surface for alanine tripeptide in water using FERRMap and found 61 equilibrium structures (EQ) connected by 133 TS points. After elucidating the MFEP network, we analysed the structures of the EQ points and the MFEPs connecting beta-sheet structures and beta-turn structures or left-handed helix structures.

GRAPHICAL ABSTRACT

KEYWORDS:

• Minimum free energy path
• molecular dynamics simulation
• umbrella sampling
• scaled hypersphere search

Acknowledgements

The computations were performed at the Research Institute for Information Technology (Kyushu University) and the supercomputer of ACCMS (Kyoto University). This research was supported by JSPS KAKENHI (Grant Number JP16J01692) and partly used computational resources under Collaborative Research Program for Young · Women Scientists provided by Academic Center for Computing and Media Studies, Kyoto University.

Disclosure statement

No potential conflict of interest was reported by the authors.

ORCID

Yuki Mitsuta http://orcid.org/0000-0002-5736-5057

Additional information

Funding

This work was supported by Japan Society for the Promotion of Science [Grant Number JP16J01692].