| Proton channel is an important molecular apparatus that has been found to be involved in various important biological functions, such as the ATP synthesis and biochemical "combustion." However, due to the complexity of biological systems and the unique characters of the smallest cation---proton itself---proton channel and the proton transport (PT) process in a channel environment are in general poorly understood at the atomic level. This lack of information has made interpretations of many macroscopic properties, such as proton selectivity, channel gating, and proton blocking, obscure, controversial or difficult. This thesis research is devoted into the study of proton channels and the PT process inside in them using computer simulations; in particular, it focuses on (1) further development of a multistate empirical valence bond (MS-EVB) modeling tool for explicit aqueous proton transport, (2) study of the hydration structure of an excess proton and the energetics of its transport through a minimalist yet representative synthetic LS2 channel, and (3) study of the possible closed and open states of the M2 channel from the influenza A virus. The model-development effort has resulted in an improved MS-EVB model. The study on the LS2 channel has provided atomistic description of the hydrated excess proton inside a typical channel environment and energetic basis for the proton selectivity of the LS2 channel. The study on the M2 channel has resulted in new insight of the detailed structures of the closed and open states of the M2 channel and a proposal of a revised gating mechanism for this proton channel. |
