Finite Temperature String Method with Umbrella Sampling: Application on a Side Chain Flipping in Mhp1 Transporter
dc.contributor.author | Song, Hyun Deok | |
dc.contributor.author | Zhu, Fangqiang | |
dc.contributor.department | Physics, School of Science | en_US |
dc.date.accessioned | 2018-01-18T19:26:27Z | |
dc.date.available | 2018-01-18T19:26:27Z | |
dc.date.issued | 2017 | |
dc.description.abstract | Protein conformational change is of central importance in molecular biology. Here we demonstrate a computational approach to characterize the transition between two metastable conformations in all-atom simulations. Our approach is based on the finite temperature string method, and the implementation is essentially a generalization of umbrella sampling simulations with Hamiltonian replica exchange. We represent the transition pathway by a curve in the conformational space, with the curve parameter taken as the reaction coordinate. Our approach can efficiently refine a transition pathway and compute a one-dimensional free energy as a function of the reaction coordinate. A diffusion model can then be used to calculate the forward and backward transition rates, the major kinetic quantities for the transition. We applied the approach on a local transition in the ligand-free Mhp1 transporter, between its outward-facing conformation and an intermediate conformation with the side chain of Phe305 flipped to the outside of the protein. Our simulations predict that the flipped-out position of this side chain has a free energy 6.5 kcal/mol higher than the original position in the crystal structure, and that the forward and backward transition rates are in the millisecond and submicrosecond time scales, respectively. | en_US |
dc.eprint.version | Author's manuscript | en_US |
dc.identifier.citation | Song, H. D., & Zhu, F. (2017). Finite Temperature String Method with Umbrella Sampling: Application on a Side Chain Flipping in Mhp1 Transporter. The Journal of Physical Chemistry B, 121(15), 3376–3386. https://doi.org/10.1021/acs.jpcb.6b08568 | en_US |
dc.identifier.uri | https://hdl.handle.net/1805/15023 | |
dc.language.iso | en | en_US |
dc.publisher | ACS | en_US |
dc.relation.isversionof | 10.1021/acs.jpcb.6b08568 | en_US |
dc.relation.journal | The Journal of Physical Chemistry B | en_US |
dc.rights | IUPUI Open Access Policy | en_US |
dc.source | Author | en_US |
dc.subject | protein conformational change | en_US |
dc.subject | finite temperature string method | en_US |
dc.subject | umbrella sampling simulations | en_US |
dc.title | Finite Temperature String Method with Umbrella Sampling: Application on a Side Chain Flipping in Mhp1 Transporter | en_US |
dc.type | Article | en_US |