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oai:figshare.com:article/33435397 2026-10-01T16:34:25Z category_1 category_7 category_12 category_13 category_15 category_16 category_21 category_873 category_734 category_931 category_811 portal_63 item_type_6 month_year_10_2026

Current–Voltage Characteristics of K+ Channels Estimated by MD Simulations and Markov State Models Simone Furini (173392) Luigi Catacuzzeno (125929) Biophysics Medicine Cell Biology Genetics Neuroscience Physiology Biotechnology Chemical Sciences not elsewhere classified Biological Sciences not elsewhere classified Information Systems not elsewhere classified Mathematical Sciences not elsewhere classified yielded important insights whose voltage dependence rate theory formulation markov state models high computational cost limits direct comparison membrane potentials well low membrane potentials time rate matrices potassium channels kcsa md simulations performed membrane potentials potassium channels typically performed quantitative comparison membrane potential ion channels channels estimated physiological values obtained directly necessarily linear modeled using limited number ion conduction good agreement currents predicted channel currents Molecular dynamics (MD) simulations have yielded important insights into ion conduction in potassium channels, but quantitative comparison with electrophysiological experiments remains challenging. Due to their high computational cost, MD simulations are typically performed at membrane potentials well above physiological values, and at only a limited number of voltages. Since current–voltage relationships are not necessarily linear, this limits direct comparison between simulations and experiments. Here, we introduce a method to estimate the current–voltage characteristics of ion channels from Markov state models (MSMs) constructed from MD simulations performed at only few membrane potentials. Time-discrete MSMs of ion conduction are converted into continuous-time rate matrices, whose voltage dependence is modeled using a rate theory formulation with free energy barriers depending on membrane potential. This approach enables the prediction of channel currents over a wide voltage range without additional simulations. We validated the method using MD simulations of the potassium channels KcsA and MthK. In both cases, the currents predicted at low membrane potentials are in good agreement with those obtained directly from MD simulations, demonstrating the robustness and efficiency of the approach. 2026-09-28T00:00:00Z Text Journal contribution 10.1021/acs.jcim.6c01258.s001 https://figshare.com/articles/journal_contribution/Current_Voltage_Characteristics_of_K_Channels_Estimated_by_MD_Simulations_and_Markov_State_Models/33435397 CC BY-NC 4.0