TASK DEFINITION: In this task, you're given a paragraph and title from the research paper. Your task is to classify whether the given title is suitable or not for the research paper based on the given paragraph. Return "True" if title is proper according to paragraph else "False".
PROBLEM: Paragraph: The new era in systems pharmacology has revolutionized the human biology. Its applicability, precise treatment, adequate response and safety measures fit into all the paradigm of medical/clinical practice. The importance of mathematical models in understanding the disease pathology and epideomology is now being realized. The advent of high-throughput technologies and the emergence of systems biology have resulted in the creation of systems pharmacogenomics and the focus is now on personalized medicine. However, there are some regulatory issues that need to be addresssed; are we ready for this universal adoption? This article details some of the infectious disease pharmacogenomics to the developments in this area. 
 Title: System pharmacogenomics application in infectious diseases

SOLUTION: True

PROBLEM: Paragraph: Bluetongue virus (BTV) encodes a single capping protein, VP4, which catalyzes all reactions required to generate cap1 structures on nascent viral transcripts. Further, structural analysis by X-ray crystallography indicated each catalytic reaction is arranged as a discrete domain, including a nucleoside-2 0 -O-methyltransferase (2 0 -O MTase). In this study, we have exploited the structural information to identify the residues that are important for the catalytic activity of 2 0 -O MTase of VP4 and their influence on BTV replication. The effect of these mutations on GMP binding, guanylyltransferase (GTase) and methylase activities were analysed by a series of in vitro biochemical assays using recombinant mutant proteins; subsequently their effects on virus replication were assessed by introducing the same mutations in replicating viral genome using a reverse genetics system. Our data showed that single substitution mutations in the catalytic tetrad K-D-K-E were sufficient to abolish 2 0 -O MTase activity in vitro and to completely abrogate BTV replication in cells; although these mutants retained the upstream GMP binding, GTase and guanine-N7-methyltransferase activities. Mutations of the surrounding substrate-binding pocket (predicted to recruit cap0) had variable effects on in vitro VP4 capping activity. Only triple but not single substitution mutations of these residues in genome resulted in reduced virus replication kinetics. This is the first report investigating the importance of 2 0 -O MTase function for any member of the Reoviridae and highlights the significance of K-D-K-E tetrad and surrounding residues for the efficiency of 2 0 -O MTase activity and in turn, for virus fitness. 
 Title: Structure-based identification of functional residues in the nucleoside- 2 0 -O-methylase domain of Bluetongue virus VP4 capping enzyme-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

SOLUTION: True

PROBLEM: Paragraph: Chemical denaturant sensitivity of the dimeric main protease from severe acute respiratory syndrome (SARS) coronavirus to guanidinium chloride was examined in terms of fluorescence spectroscopy, circular dichroism, analytical ultracentrifuge, and enzyme activity change. The dimeric enzyme dissociated at guanidinium chloride concentration of ,0.4 M, at which the enzymatic activity loss showed close correlation with the subunit dissociation. Further increase in guanidinium chloride induced a reversible biphasic unfolding of the enzyme. The unfolding of the C-terminal domain-truncated enzyme, on the other hand, followed a monophasic unfolding curve. Different mutants of the full-length protease (W31 and W207/W218), with tryptophanyl residue(s) mutated to phenylalanine at the C-terminal or N-terminal domain, respectively, were constructed. Unfolding curves of these mutants were monophasic but corresponded to the first and second phases of the protease, respectively. The unfolding intermediate of the protease thus represented a folded C-terminal domain but an unfolded N-terminal domain, which is enzymatically inactive due to loss of regulatory properties. The various enzyme forms were characterized in terms of hydrophobicity and size-and-shape distributions. We provide direct evidence for the functional role of C-terminal domain in stabilization of the catalytic N-terminal domain of SARS coronavirus main protease. 
 Title: Reversible Unfolding of the Severe Acute Respiratory Syndrome Coronavirus Main Protease in Guanidinium Chloride

SOLUTION:
True