Viruses data processing

Tsuruta, H., et al. (1998). Imaging RNA and dynamic protein segments with low-resolution virus crystallography experimental design, data processing and imph-cations of electron density maps. /. Mol. Biol. 284, 1439-1452. 

PDB is one of the oldest protein data bases, founded in 1971. It has three locations, Rutgers University in New Jersey, San Diego Supercomputer Center (SDSC) at the University of California, and the National Institute of Standards and Technology (NIST) in Gaithersburg, Maryland. The PDB is a source for protein characterization and structure as well. The PDB archive contains macromolecular structure data on proteins, nucleic acids, protein-nucleic acid complexes, and viruses. Approximately 50-100 new structures are deposited each week, which are annotated and released upon the depositor s specifications. PDB data are freely available worldwide. PDB formats, annotates, validates, and releases dozens of complicated structure files each week some of them take only a couple of hours, others take weeks to process. Data processing is the main task of people at the PDB and validation is the most time-consuming part (Smith-Schmidt, 2002). 

Process validation starts with the identification of product quality attributes and justification of acceptance criteria, followed by a review of the risk analysis, execution of process development runs, and compilation of clinical material manufacturing data to set specifications considering process variability [11]. There is a greater focus on process validation for downstream steps rather than for upstream steps because downstream steps are associated with virus removal. Process validation is just one approach used to control virus contamination, however others include cell bank characterization, in-process testing, inactivation procedures, control of raw materials, containment, and postmarket surveillance [6]. 

The HlV-1 protease is responsible for processing the protein precursors to the enzymes (integrase, protease and reverse transcriptase) and the structural proteins of the HIV-1 virus. Maw and Hall found that topological indices provide rehable QSAR models for the IC50 data of 32 HIV-1 protease inhibitors [29]. The best QSAR model, with r = 0.86, s=0.60 and q = 0.79, was obtained with the shape index Ka, the connechvity index the sum of HE-state indices for ah groups that act as... 

It is clear that this approach does not deliver information about the binding process at atomic resolution. Rather, it focuses on the binding affinities of ligands to the virus. Careful data analysis allows discrimination of residues that actively participate in the binding from those that contribute less to the interaction. Ligands in the intermediate exchange regime on the chemical... 

The virus reduction factor of an individual purification or removal—inactivation step is defined as the log10 of the ratio of the virus load in the pre-purification material divided by the virus load in the post-purification material. A clearance factor for each stage can be calculated and the overall clearance capacity of the production process assessed. Total virus reduction is calculated as the sum of individual log reduction factors. Individual manufacturing steps must possess fundamentally different mechanisms of virus removal or inactivation in order for values to be considered cumulative. Additionally, because viruses vary greatly with regard to inactivation or removal profiles, only data for the same model virus can be cumulative. 

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