A New Computer Model for Evaluating the Selective Binding Affinity of Phenylalkylamines to T-Type Ca²⁺ Channels

Abstract

To establish a computer model for evaluating the binding affinity of phenylalkylamines (PAAs) to T-type Ca2+ channels (TCCs), we created new homology models for both TCCs and a L-type calcium channel (LCC). We found that PAAs have a high affinity for domains I and IV of TCCs and a low affinity for domains III and IV of the LCC. Therefore, they should be considered as favorable candidates for TCC blockers. The new homology models were validated with some commonly recognized TCC blockers that are well characterized. Additionally, examples of the TCC blockers created were also evaluated using these models.

Keywords

• T-type calcium channel blocker
• homology modeling
• computer-aid drug design
• virtual drug screening
• L-type calcium channel