Abstract: Provided herein are systems and methods for selecting compounds that have reduced risk of cardiotoxicity or which are not likely to be cardiotoxic. As an example, a system and method can include a computational dynamic model combined with a high throughput screening in silico that mimics an important ion channels associated with cardiotoxicity, namely the human cardiac sodium ion (hNav1.5) channel). In certain embodiments, steered molecular dynamics simulations are used to identify key residues of the channel's permeation pathways that are then used in the high throughput screening. Also provided herein are systems and methods for redesigning compounds that are predicted to be cardiotoxic based on the model and the high throughput screening.