Structure and Dynamics of SARS Coronavirus Proteinase: The Primary Key to the Designing and Screening for Anti-SARS Drugs

Abstract

Structure and dynamics of SARS coronavirus (SARS-CoV) proteinase have been investigated using molecular dynamics (MD) simulation technique. The simulations were carried out under the NPT ensemble at 298 K and 1 atm, for free enzyme in both monomer and dimer forms and the monomer-inhibitor complex. The systems were observed to reach equilibrium after 200 ps. Enzyme conformation and its structural changes were monitored in terms of root mean square displacement of all 306 amino acid residues. The results show, as expected, that the proteinase in complex form is, in average, less flexible than the free form. Interest is centered on the two regions, at N-termini (residues 1-2) and around the active site (residues 56-62), in which the flexibilities in complex form is lower than those in free form. This behavior is supposed to facilitate the binding between enzyme and substrate. With the obtained MD structure, molecular dockings have been carried out in order to search for potent SARS-CoV proteinase inhibitors. Preliminary results show that among sixteen antiviral drugs taken from the NCI database, four of them with trade-name Nevirapine, Glycovir, Virazole, and Calanolide A, are observed to fit well in the active site of the SARS-CoV proteinase.