Exploring Conformational Transition of 2019 Novel Coronavirus Spike Glycoprotein Between Its Closed and Open States Using Molecular Dynamics Simulations

Mert Gur; Elhan Taka; Sema Zeynep Yilmaz; Ceren Kilinc; Umut Aktas; Mert Golcuk

Recently, the crystal structure of RBD bound to ACE2 was resolved at 2.45 Ã… resolution (PDB ID: 6M0J (Lan et al. 2020) ). Based on this structure, RBD amino acids K417, G446, Y449, Y453, L455, F456, A475, F486, N487, Y489, Q493, G496, Q498, T500, N501, G502, Y505 (locations shown in Fig. 5 ) are interacting with ACE2. In order to investigate the solvent accessibility of these amino acids, close contact water molecules were calculated for the closed and open state MD simulations. To this aim, water molecules within 5 Ã… of the RBD amino acids involved in ACE2 binding were evaluated for each protein conformation sampled in the MD simulations. Notably, while the number of close contact water molecules were 433 for RBD in up position on average, the number of close contact water molecules was only 296 for RBD in down position of the closed state. As shown in Fig. 5(a) , the RBDs of the S protein trimer are closely packed in the closed state, hence strongly limiting water accessibility to amino acids K417, Y453, L455, F456, and Y505. The remaining amino acids G446, Y449, A475, F486, N487, Y489, Q493, G496, Q498, T500, N501, and G502 are solvent accessible and could potentially be accessed by small molecules in the closed state of S protein.