Interconnected Key Factors in Biomolecule Structure Determination: From Experiment to Comprehensive Understanding

Quite intriguingly, the key factors included in Figure~/ref{fig:77733key} are interlinked to one another. Starting from experimental structure determination, where experimental techniques such as X-ray crystallography, NMR spectroscopy, cryo-electron microscopy (cryo-EM), or Cryo-electron tomography (cryo-ET) /cite{Li2023cryo-ET,Eisenstein2023} are used to record direct experimental data, e.g., X-ray diffraction pattern, chemical shift, cryo-EM images, or Cryo-ET tomographies. Afterwards, structure calculation methods are used to refine and interpret the experimental data, which involve mathematical algorithms and computational structural modeling to provide the initial atomic coordinates, with which the forcefield Figure~/ref{fig:77733key} describes the interactions between atoms. Subsequently, energy minimization optimizes the atomic positions to find the lowest energy configuration, and to generate an accurate and complete representation of the biomolecule's structure./n/nIn short, these factors (Figure~/ref{fig:77733key}) are interlinked, forcefield, atomic coordinates, structural information, PTM, PEM, /pKa, and energy minimization all rely on each other to obtain a comprehensive understanding of the biomolecule's structure and properties. Experimental techniques provide direct data, which is then used in structure calculation methods to generate initial atomic coordinates. The forcefield describes the interactions between atoms, which is crucial for energy minimization to find the lowest energy configuration. This process ultimately leads to a complete representation of the biomolecule's structure, allowing for further analysis of factors such as post-translational modifications (PTM), protein-protein interaction (PEM), and the calculation of protonation states (/pKa). Overall, these key factors work together to unravel the complex structure and behavior of biomolecules.