Including crystallographic symmetry in quantum-based refinement: Q|R#2.
Min ZhengMalgorzata BiczyskoYanting XuNigel W MoriartyHolger KruseAlexandre UrzhumtsevMark P WallerPavel V AfoninePublished in: Acta crystallographica. Section D, Structural biology (2020)
Three-dimensional structure models refined using low-resolution data from crystallographic or electron cryo-microscopy experiments can benefit from high-quality restraints derived from quantum-chemical methods. However, nonperiodic atom-centered quantum-chemistry codes do not inherently account for nearest-neighbor interactions of crystallographic symmetry-related copies in a satisfactory way. Here, these nearest-neighbor effects have been included in the model by expanding to a super-cell and then truncating the super-cell to only include residues from neighboring cells that are interacting with the asymmetric unit. In this way, the fragmentation approach can adequately and efficiently include nearest-neighbor effects. It has previously been shown that a moderately sized X-ray structure can be treated using quantum methods if a fragmentation approach is applied. In this study, a target protein (PDB entry 4gif) was partitioned into a number of large fragments. The use of large fragments (typically hundreds of atoms) is tractable when a GPU-based package such as TeraChem is employed or cheaper (semi-empirical) methods are used. The QM calculations were run at the HF-D3/6-31G level. The models refined using a recently developed semi-empirical method (GFN2-xTB) were compared and contrasted. To validate the refinement procedure for a non-P1 structure, a standard set of crystallographic metrics were used. The robustness of the implementation is shown by refining 13 additional protein models across multiple space groups and a summary of the refinement metrics is presented.
Keyphrases
- molecular dynamics
- high resolution
- single cell
- monte carlo
- density functional theory
- cell therapy
- healthcare
- single molecule
- induced apoptosis
- protein protein
- electron microscopy
- heart failure
- big data
- stem cells
- computed tomography
- molecular dynamics simulations
- optical coherence tomography
- minimally invasive
- artificial intelligence
- amino acid
- binding protein
- atrial fibrillation
- mass spectrometry
- electronic health record
- machine learning
- bone marrow
- cell death
- small molecule
- newly diagnosed
- oxidative stress
- label free
- acute heart failure