Free Energy Change during the Formation of Crystalline Contact between Lysozyme Monomers under Different Physical and Chemical Conditions

Abstract

We use the MM/GBSA method to calculate the free energies of dimer formation by binding two monomers with different combinations of precipitant ions, both embedded in the structure of monomers and in the crystallization solution. It shows that the largest difference in free energy values corresponds to the most accurate dimer model, which considers all precipitant ions in their structure. In addition, it shows that in the absence of precipitant ions in the solution of lysozyme molecules, a monomer is a more energetically favorable state.

The Role of Cations and Anions in the Formation of Crystallization Oligomers in Protein Solutions as Revealed by Combination of Small-Angle X-ray Scattering and Molecular Dynamics

“…Moreover, it is known that protein crystallization mainly depends on the precipitant anions that are chloride ions in the case of lysozyme [1]. Interestingly, the dimer formation with only sodium cation associated with lysozyme is slightly more energetically favorable than it is when all precipitant ions (three sodium and four chlorides) are embedded at NaCl concentrations of 0.4 and 0.6 M [10]. At 0.4 M NaCl in solution, change in free energy upon the binding of lysozyme monomers calculated by MM/GBSA method was −7.87 kcal/M in the case that only Na + ions were taken into account, while it was −7.78 kcal/M when Na + and Cl − were incorporated.…”

“…Therefore, the correspondence of molecular dynamics results to the temperature investigations of tetragonal lysozyme crystallization solutions by SAXS is achieved only by taking into account all precipitant ions in calculations. In addition, dimers remain more stable with precipitant ions (at least anions) embedded in the protein than without them [10]. However, a model with only one sodium ion was used to process the same data [4].…”

Self-Assembly and Conformational Change in the Oligomeric Structure of the Ectodomain of the TBEV E Protein Studied via X-ray, Small-Angle X-ray Scattering, and Molecular Dynamics

“…The absence of irregular aggregates is a necessary baseline criterion that samples should meet. In some works, it was shown that when a precipitant used in crystallization is added to proteins, the oligomers formed in the solution are the structural units of the growing crystal [16,17]. There are also examples when a high protein concentration and a certain pH are sufficient for crystallization [18], suggesting the formation of oligomers that serve as 'nucleation precursors' for crystal formation [19].…”