The continuous evolution of SARS-CoV-2SARS-CoV-2 spike proteinSpike protein (S-protein) and emergence of new mutationsMutations was inevitable and highlighted the importance of protein modelling methods in rationalizing and predicting such events. The ability of spike proteinSpike protein to bind human ACE2 receptor and evade antibodies depends on its structure and variable conformations. Here, we discussed the vast data of SARS-CoV-2SARS-CoV-2 S-protein structures and how the availability of these structures facilitated analysis of viral function and evolution. We analyzed the S-protein in apo and holo forms using structure-based methods. The holo form included the S-protein bound to ACE2 and antibody structures. We explained the significance of using multiple high quality input structures and averages of a group to model mutationMutations effect in order to understand structural heterogeneityStructural heterogeneity effect and reduce systematic errors and biases. We noted that several mutations that occurred in the receptor binding domain (RBD) of S-protein increased charge, possibly to adapt negatively charge surface of ACE2 receptor. We proposed a simple fitness modelFitness model based on the two very simple properties of S-protein binding to ACE2 and antibody ensemble. Our study demonstrates substantial challenges and indicate ways to develop improved computational tools that could assist in understanding and predicting the evolution of the SARS-CoV-2SARS-CoV-2 S-protein.