title: Towards New Drug Targets? Function Prediction of Putative Proteins of Neisseria meningitidis MC58 and Their Virulence Characterization.
abstract: Neisseria meningitidis is a Gram-negative aerobic diplococcus, responsible for a variety of meningococcal diseases. The genome of N. meningitidis MC58 is comprised of 2114 genes that are translated into 1953 proteins. The 698 genes (∼35%) encode hypothetical proteins (HPs), because no experimental evidence of their biological functions are available. Analyses of these proteins are important to understand their functions in the metabolic networks and may lead to the discovery of novel drug targets against the infections caused by N. meningitidis. This study aimed at the identification and categorization of each HP present in the genome of N. meningitidis MC58 using computational tools. Functions of 363 proteins were predicted with high accuracy among the annotated set of HPs investigated. The reliably predicted 363 HPs were further grouped into 41 different classes of proteins, based on their possible roles in cellular processes such as metabolism, transport, and replication. Our studies revealed that 22 HPs may be involved in the pathogenesis caused by this microorganism. The top two HPs with highest virulence scores were subjected to molecular dynamics (MD) simulations to better understand their conformational behavior in a water environment. We also compared the MD simulation results with other virulent proteins present in N. meningitidis. This study broadens our understanding of the mechanistic pathways of pathogenesis, drug resistance, tolerance, and adaptability for host immune responses to N. meningitidis.
authors.affiliation: 1 Department of Chemistry, Durban University of Technology , Durban, South Africa .
authors.forename: Mohd
authors.initials: M
authors.lastname: Shahbaaz
authors.affiliation: 1 Department of Chemistry, Durban University of Technology , Durban, South Africa .
authors.forename: Krishna
authors.initials: K
authors.lastname: Bisetty
authors.affiliation: 2 Center for Interdisciplinary Research in Basic Sciences , Jamia Millia Islamia, Jamia Nagar, New Delhi, 110025, India .
authors.forename: Faizan
authors.initials: F
authors.lastname: Ahmad
authors.affiliation: 2 Center for Interdisciplinary Research in Basic Sciences , Jamia Millia Islamia, Jamia Nagar, New Delhi, 110025, India .
authors.forename: Md Imtaiyaz
authors.initials: MI
authors.lastname: Hassan
mesh_terms: D019295:Computational Biology / Q000379:methods; D015195:Drug Design; D016679:Genome, Viral; D056004:Molecular Dynamics Simulation; D009345:Neisseria meningitidis / Q000472:pathogenicity*; D017434:Protein Structure, Tertiary; D020539:Sequence Analysis, Protein; D013329:Structure-Activity Relationship; D014764:Viral Proteins / Q000737:chemistry*; D037521:Virulence Factors / Q000737:chemistry*
chemical_list: D014764:Viral Proteins; D037521:Virulence Factors