Pandjassarame Kangueane

Christina Nilofer

Vellore Institute of Technology (VIT) is a private university located in&nbsp;Tamil Nadu, India. Founded in 1984, as Vellore Engineering College, the institution offers 20 undergraduate, 34 postgraduate, four integrated and four research programs. It has campuses in Vellore, Amravati, Bhopal and Chennai.

VIT is one of the top ranked private universities in India according to NIRF, THE and QS Rankings.&nbsp;Govt. of India has recognized&nbsp;VIT, Vellore as an&nbsp;Institution of Eminence. This has allowed VIT to take independent quality initiatives and move up in world ranking.

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VIT University

Protein-Protein and Domain-Domain Interactions

HLA-Peptide Interaction to Short Peptide Vaccine Design

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Bioinformation

Protein-protein interfaces are vdW dominant with selective H-bonds and (or) electrostatics towards broad functional specificity

The development of an HIV-1/AIDS vaccine has posed great challenges over the last two decades to the international scientific community. The synthesis of a viable vaccine component has gained momentum in recent years after several learning stories with partial success. The moderate efficacy showed by RV144 (ENV-gp120, Gag and Pro) vaccine (Thai trial vaccine) in clinical trials provided impetus to the study during the last decade. The technological challenge in the production of the viral spike as a viable vaccine component is realized since the conclusion of the Thai trial (2009). The results from the NIAID-sponsored South African HVTN 702 (ALVAC-HIV + subtype C gp120/MF59 2700) trial are awaited. The HIV-1 envelope spike [ENV GP160 trimer complex] is being exploited as a promising vaccine candidate in recent years. A number of knowledge points on the viral spike are now available using data derived from several disciplines of biotechnology. The production of a native conformation of the HIV-1 ENV GP160 trimer SPIKE with appropriate glycosylation taking into consideration about 39,000 variants of known GP160 sequences among known subtypes (as available at the LANL database) is found to be nontrivial. The known HIV-1 ENV GP160 trimer SPIKE electron microscopy structure at 4.19 resolution shows nine interfaces with three different types. Their characteristic features are interesting towards the development of a stable yet effective trimer complex. The GP41-GP41 and GP41-GP120 interfaces are characteristics of equal polar to non-polar residues, and the GP120-GP120 interfaces are predominantly polar in nature. These data find application in the development of an immunologically viable vaccine component. © Springer Science+Business Media LLC 2017.

Global Virology II - HIV and NeuroAIDS

HIV-1 Envelope (ENV) GP160 Trimer Protein Complex SPIKE as a Recombinant Macromolecular Assembly Vaccine Component Candidate: Current Opinion

The homodimers have essential role in catalysis and regulation. The homodimer folding mechanism through 2-state without stable intermediate (2S), 3-state with monomer intermediate (3SMI) and 3-state with dimer intermediate (3SDI) is fascinating. 23MI and 3SDI constitute 3-state (3S). Hence, it is important to differentiate 2S, 3SMI and 3SDI homodimers using structural features. We used the dataset of Li et al. [L. Li, K. Gunasekaran, J.G. Gan, C. Zhanhua, P. Shapshak, M.K. Sakharkar, P. Kangueane, Structural features differentiate the mechanisms between 2S and 3S folding of homodimers, Bioinformation 1 (2005) 42-49] consisting of twenty-five 2S, ten 3SMI and six 3SDI homodimer structures for the study. Interface to total (I/T) residues ratio is large for 2S than 3SMI and 3SDI. Interface to total residues ratio is similar for 3SMI (mean monomer length (ML) = 208) and 3SDI (mean monomer length (ML) = 404) despite difference in mean monomer size. Interface residues correlate with monomer size in 2S (Pearson's correlation coefficient (r); r2 = 0.41) and 3SMI (r2 = 0.52). This is not true for 3SDI with interface residues and monomer length (r2 = 0.17). Interface area (B/2) does not correlate with interface residues (r2 &lt; 0.001) and monomer size (r2 = 0.023) in 2S. This is despite a relationship with interface residues and monomer size (r2 = 0.41) in 2S. However, this is not true for 3SMI (r2 = 0.61 with interface residues and r2 = 0.25 with monomer size). In 3SDI, a different relationship is seen (r2 = 0.28 with interface residues and r2 = 0.09 with size). The mean hydrophobicity factor (Hf) is 3-fold less in 3S than 2S. Hf does not correlate with interface area in 2S (r2 = 0.03) and 3SDI (r2 = 0.0). However, a weak causal relation is seen in 3SMI (r2 = 0.23). Hydrophilic amino acid residues (E, R, K, S and Q) are prominent in 2S than 3S. Charged negative amino acid residues (D, E) are more than positive amino acid residues (R, K, H) in 2S and charged positive amino acid residues (R, K, H) are more than negative amino acid residues (D, E) in 3S. These features help to distinguish 2S, 3SMI and 3SDI providing insights to homodimer folding and binding. © 2009 Elsevier Inc. All rights reserved.

Journal of Molecular Graphics and Modelling

Structural features for homodimer folding mechanism

The precise prediction of class II human leukocyte antigen (HLA) peptide binding finds application in epitope design for the development of vaccines and diagnostics of diseases associated with CD4+ T-cellular immunity. HLA II binding peptides have an extended conformation at the binding groove unlike class I. This increases peptide binding combinations of varying length at the groove, having an eventual effect in the host immune response to infectious agents. Here we describe the development of a prediction model using information gleaned from HLA II-peptide (HLA II-p) structural data. We created a manually curated dataset of 15 HLA II-p structural complexes from Protein databank (PDB). The dataset was used to develop virtual binding pockets for accommodating HLA-II-specific short peptides. The binding of peptides to the virtual pockets is estimated using the Q matrix (a quantitative matrix based on amino acid residue properties). Internal cross-validation of the model using the 15 HLA II-p structural complexes produced an accuracy of 53% with a sensitivity of 53%. The model was further evaluated using a dataset of 3676 class II-specific peptides consisting of 1188 binders and 2488 nonbinders derived from MHCBN (a database of HLA binders and nonbinders). The model produced an accuracy of 53% with 70.8% specificity and 27.6% sensitivity. The positive predictive value (PPV) was 62% and the negative predictive value (NPV) 58%. A 62% PPV suggests that the model fairly predicts a good number of binders among predicted binders and thus that the success rate among predicted binder for further verification is good. The described model is simple and rapid, with large HLA allele coverage representing the sampled global population, despite weak prediction accuracy. The ability of the model to predict a wide array of defined class II alleles is found to be applicable for proteome-wide scanning of parasitic genomes. © 2009 American Society for Histocompatibility and Immunogenetics.

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