We developed and applied a computational approach to simulate functional effects of the global circulating mutation D614G of the SARS-CoV-2 spike protein. All-atom molecular dynamics simulations are combined with deep mutational scanning and analysis of the residue interaction networks to investigate conformational landscapes and energetics of the SARS-CoV-2 spike proteins in different functional states of the D614G mutant. The results of conformational dynamics and analysis of collective motions demonstrated that the D614 site plays a key regulatory role in governing functional transitions between open and closed states. Using mutational scanning and sensitivity analysis of protein residues, we identified the stability hotspots in the SARS-CoV-2 spike structures of the mutant trimers. The results suggest that the D614G mutation can induce the increased stability of the open form acting as a driver of conformational changes, which may result in the increased exposure to the host receptor and promote infectivity of the virus. The network community analysis of the SARS-CoV-2 spike proteins showed that the D614G mutation can enhance long-range couplings between domains and strengthen the interdomain interactions in the open form, supporting the reduced shedding mechanism. This study provides the landscape-based perspective and atomistic view of the allosteric interactions and stability hotspots in the SARS-CoV-2 spike proteins, offering a useful insight into the molecular mechanisms underpinning functional effects of the global circulating mutations.