Structure, interface stability and hot-spots identification for RBD(SARS-CoV-2):hACE2 complex formation

Abstract

The nature of intermolecular interactions between the SARS-CoV-2 receptor binding domain (RBD) and its receptor, human angiotensin-converting enzyme 2 (hACE2) has been investigated by Langevin simulations to provides clarity from a dynamic and energetic point of view. Hinge prediction and cross-correlation matrix analysis by elastic network models were applied to better understand the interface dynamics that promote the interdomain surface complementarity adjustment. Main results regarding dynamic aspects indicate that there is a large network of different types of interactions i.e. hydrogen bonding, salt bridges and numerous hydrophobic interactions stabilising the complex. With respect to the energetic aspects, we identified and evaluated the energy strength of the primary amino acids involved in the interaction that likely stabilise complex formation. Our results indicate that Tyr449, Leu455, Phe456, Ala475, Phe486, Gln493, Gly496, Gln498, Thr500, Asn501, Gly502, and Tyr505 form the primary interface between the SARS-CoV-2 RBD and hACE2.