BIOE 402. Medical Technology Assessment. 2 or 3 hours. Bioentrepreneur course. Assessment of medical technology in the context of commercialization. Objectives, competition, market share, funding, pricing, manufacturing, growth, and intellectual property; many issues unique to biomedical products. Course Information: 2 undergraduate hours. 3 graduate hours. Prerequisite(s): Junior standing or above and consent of the instructor.

“Bioinformatics” 특집을 내면서

Protein–protein interaction (PPI) establishes the central basis for complex cellular net-works in a biological cell. Association of proteins with other proteins occurs at varying affinities,yet with a high degree of specificity. PPIs lead to diverse functionality such as catalysis, regulation,signaling, immunity, and inhibition, playing a crucial role in functional genomics. The molecularprinciple of such interactions is often elusive in nature. Therefore, a comprehensive analysis ofknown protein complexes from the Protein Data Bank (PDB) is essential for the characterization ofstructural interface features to determine structure–function relationship. Thus, we analyzed a non-redundant dataset of 278 heterodimer protein complexes, categorized into major functionalclasses, for distinguishing features. Interestingly, our analysis has identified five key features(interface area, interface polar residue abundance, hydrogen bonds, solvation free energy gainfrom interface formation, and binding energy) that are discriminatory among the functional classesusing Kruskal-Wallis rank sum test. Significant correlations between these PPI interface featuresamongst functional categories are also documented. Salt bridges correlate with interface area inregulator-inhibitors (r50.75). These representative features have implications for the prediction ofpotential function of novel protein complexes. The results provide molecular insights for betterunderstanding of PPIs and their relation to biological functions.Keywords: protein–protein interaction; heterodimers; surface; interface; protein structure; proteinfunctionIntroduction

Linking structural features of protein complexes and biological function.

Molecular function in cellular processes is governed by protein-protein interactions (PPIs) within biological networks. Selective yet specific association of these protein partners contributes to diverse functionality such as catalysis, regulation, assembly, immunity, and inhibition in a cell. Therefore, understanding the principles of protein-protein association has been of immense interest for several decades. We provide an overview of the experimental methods used to determine PPIs and the key databases archiving this information. Structural and functional information of existing protein complexes confers knowledge on the principles of PPI, based on which a classification scheme for PPIs is then introduced. Obtaining high-quality non-redundant datasets of protein complexes for interaction characterisation is an essential step towards deciphering their underlying binding principles. Analysis of physicochemical features and their documentation has enhanced our understanding of the molecular basis of protein-protein association. We describe the diverse datasets created/collected by various groups and their key findings inferring distinguishing features. The currently available interface databases and prediction servers have also been compiled.

Protein-protein interactions and prediction: a comprehensive overview.

Metabolic variations in seaweed, Sargassum polycystum samples subjected to different drying methods via 1H NMR-based metabolomics and their bioactivity in diverse solvent extracts

A site for direct integrin αvβ6·uPAR interaction from structural modelling and docking.

Protein heterodimer complexes are often involved in catalysis, regulation, assembly, immunity and inhibition. This involves the formation of stable interfaces between the interacting partners. Hence, it is of interest to describe heterodimer interfaces using known structural complexes. We use a non-redundant dataset of 192 heterodimer complex structures from the protein databank (PDB) to identify interface residues and describe their interfaces using amino-acids residue property preference. Analysis of the dataset shows that the heterodimer interfaces are often abundant in polar residues. The analysis also shows the presence of two classes of interfaces in heterodimer complexes. The first class of interfaces (class A) with more polar residues than core but less than surface is known. These interfaces are more hydrophobic than surfaces, where protein-protein binding is largely hydrophobic. The second class of interfaces (class B) with more polar residues than core and surface is shown. These interfaces are more polar than surfaces, where binding is mainly polar. Thus, these findings provide insights to the understanding of protein-protein interactions.

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Insights from the structural analysis of protein heterodimer interfaces.

The human immunodeficiency virus type-1 (HIV-1) gp160 (gp120-gp41 complex) trimer envelope (ENV) protein is a potential vaccine candidate for HIV/AIDS. HIV-1 vaccine development has been problematic and charge polarity as well as sequence variation across clades may relate to the difficulties. Further obstacles are caused by sequence variation between blood and brain-derived sequences, since the brain is a separate compartment for HIV-1 infection. We utilize a threedimensional residue measure of solvent exposure, accessible surface area (ASA), which shows that major segments of gp120 and gp41 known structures are solvent exposed across clades. We demonstrate a large percent sequence polarity for solvent exposed residues in gp120 and gp41. The range of sequence polarity varies across clades, blood, and brain from different geographical locations. Regression analysis shows that blood and brain gp120 and gp41 percent sequence polarity range correlate with mean Shannon entropy. These results point to the use of protein modifications to enhance HIV-1 ENV vaccines across multiple clades, blood, and brain. It should be noted that we do not address the issue of protein glycosylation here; however, this is an important issue for vaccine design and development.

Abbreviations
HIV-1 - human immunodeficiency virus type 1, AIDS - acquired immunodeficiency syndrome, ENV - envelope, gp160 - 160,000d glycoprotein, gp120 - 120,000d glycoprotein, gp41 - 41,000d glycoprotein, LANL - Los Alamos National Laboratories, PDB - Protein Data Bank, HVTN - STEP HIV vaccine trial, AA - amino acids, MSA - multiple sequence alignment, ASA - accessible surface area, SNPs- single nucleotide polymorphisms, HAART - Highly Active Antiretroviral Therapy, CCR5 - C-C chemokine receptor type 5, CNS - central nervous system, HIVE - HIV encephalitis, P - polarity, NP - non-polarity, CTL - cytotoxic T lymphocyte, NIAID - National Institute of Allergy and Infectious Diseases.

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HIV-1 envelope accessible surface and polarity: clade, blood, and brain.

Hetero dimer (different monomers) interfaces are involved in catalysis and regulation through the formation of interface active sites. This is critical in cell and molecular biology events. The physical and chemical factors determining the formation of the interface active sites is often large in numbers. The combined role of interacting features is frequently combinatorial and additive in nature. Therefore, it is important to determine the physical and chemical features of such interactions. A number of such features have been documented in literature since 1975. However, the use of such interaction features in the prediction of interaction partners and sites given their sequences is still a challenge. In a non-redundant dataset of 156 hetero-dimer structures determined by X-ray crystallography, the interacting partners are often varying in size and thus, size variation between subunits is an important factor in determining the mode of interface formation. The size of protein subunits interacting are either small-small, largelarge, medium-medium, large-small, large-medium and small-medium. It should also be noted that the interface formed between subunits have physical interactions at N terminal (N), C terminal (C) and middle (M) region of the protein with reference to their sequences in one dimension. These features are believed to have application in the prediction of interaction partners and sites from sequences. However, the use of such features for interaction prediction from sequence is not currently clear.

/pdf/interaction-modes-at-protein-hetero-dimer-interfaces-4qhqn0flt9.pdf

Interaction modes at protein hetero-dimer interfaces.

Vaccine development for viral diseases is a challenge where subunit vaccines are often ineffective Therefore, the need for alternative solutions is crucial Thus, short peptide vaccine candidates promise effective answers under such circumstances Short peptide vaccine candidates are linear T-cell epitopes (antigenic determinants that are recognized by the immune system) that specifically function by binding human leukocyte antigen (HLA) alleles of different ethnicities (including Black, Caucasian, Oriental, Hispanic, Pacific Islander, American Indian, Australian aboriginal, and mixed ethnicities) The population-specific allele-level HLA sequence data in the public IMGT/HLA database contains approximately 12542 nomenclature defined class I (9437) and class II (3105) HLA alleles as of March 2015 present in several ethnic populations

/pdf/short-peptide-vaccine-design-and-development-promises-and-1rliavngsz.pdf

Short Peptide Vaccine Design and Development: Promises and Challenges

Interface residues stabilize protein complexes. The high energy interface residues referred as hot spots is responsible for the binding free energy of protein complexes. The characteristics of hot spots are studied using inter-atomic sidechain-sidechain interactions with reference to known alanine-mutated residues at the interface. It is known that hot spots participate in strong and energetically favorable sidechain-sidechain interactions. It should also be noted that several models are available in the literature to identify hot spots and to distinguish them from non-specific interactions at the interface.

Gopichandran Sowmya

Papers

Insights from the structural analysis of protein heterodimer interfaces.

HIV-1 envelope accessible surface and polarity: clade, blood, and brain.

Interaction modes at protein hetero-dimer interfaces.

Short Peptide Vaccine Design and Development: Promises and Challenges

Interface Hot Spots in Protein Complexes