C-H⋯.π interactions are known to be important contributors to protein stability. In this study, we have analyzed the influence of C-H⋯.π interactions in single chain "all-alpha" proteins. In the data set, a total of 181 C-H⋯.π interactions were observed. The most prominent representatives are the interactions between aromatic C-H donor groups and aromatic π acceptors. Eighty-one percent of the C-H⋯.π interactions between side chain to side chain and remaining19% of the C-H⋯.π interactions were observed between side-chain to side-chain five-member aromatic ring. The donor atom contribution to C-H⋯.π interactions was mainly from Phe, Tyr, and Trp residues. The acceptor atom contribution to C-H⋯.π interactions was mainly from Phe, Tyr, Trp, and His. The highest percentage of C-H⋯.π interactions were observed form Phe residue. The secondary structure preference analysis of all C-H⋯.π interacting residues showed that Phe, Tyr, Trp, and His preferred to be in helix. Long-range C-H⋯.π interactions are the predominant type of interactions in single chain all-alpha proteins data set. All the C-H⋯.π interactions forming residues in the data set preferred to be in the buried region. Seventy-three percent of the donor residues and 65% of the acceptor residues are highly conserved. © 2009 Humana Press.

Shanthi V

Department of Biotechnology

School of Bio Sciences and Technology

Vellore Campus

Ramanathan K

Sethumadhavan R.

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

Applied Biochemistry and Biotechnology

Neuraminidase (NA), a surface protein, facilitates the release of nascent virus and thus spreads infection. It has been renowned as a potential drug target for influenza A virus infection. The drugs such as oseltamivir, zanamivir, peramivir, and laninamivir are approved for the treatment of influenza infection. Additionally, investigational drugs namely MK2206, tamiphosphor, crenatoside, and dehydroepiandrosterone (DHEA) are also available for the treatment. However, recent outbreaks of highly pathogenic and drug-resistant influenza A strains highlighted the need to discover novel NA inhibitor. Keeping this in mind, in the current investigation, an effort was made to ascertain potent inhibitors using pharmacophore-based virtual screening and docking approach. A 3D pharmacophore model was generated based on the chemical features of approved and investigational NA inhibitors using PHASE module of Schrödinger suite. The model consists of two hydrogen bond acceptors (A), one hydrogen bond donor (D), and one positively charged group (P), AADP. Subsequently, molecules with same pharmacophoric features were screened from among the two million compounds available in the ZINC database using the generated pharmacophore hypothesis. Ligand filtration was also done to obtain an efficient collection of hit molecules by employing Lipinski “rule of five” using Qikprop module. Finally, the screened molecule was subjected to docking and molecular dynamic simulations to examine the inhibiting activity of the compounds. The results of our analysis suggest that “acebutolol hydrochloride” (156792) could be the promising candidates for the treatment of influenza A virus infection. © 2017, Springer Science+Business Media, LLC.

Discovery of Potent Neuraminidase Inhibitors Using a Combination of Pharmacophore-Based Virtual Screening and Molecular Simulation Approach

Therapeutic proteins carry out the most difficult tasks in living cells. They do so by interacting specifically with other molecules. This requires that they fold to a unique and more stable conformation. A prerequisite for comprehending the folding processes in their immense complexity entails a thorough understanding of many weak interactions. The purpose of this review is to systematically study the role of weak interactions such as cation-π, C-H......π, N-H......π and O-H......π, in the set of 49 therapeutic proteins. The importance of many of these interactions (for example, cationic residues interacting with π system) is revealed by the higher degree of conservation observed for them in protein structures. These interactions are mainly formed by long-range contacts and significant percentage of cation-π, C-H......π, N-H......π and O-H......π interacting residues had one or more stabilization centers. Further, a comparison of conventional and nonconventional interactions in the present data set unambiguously highlights the significance of these weak interactions in the structural stability of therapeutic proteins. We propose that the incorporation of the entirety of these interactions leads to a more complete description of the problem, and that this could provide new perspectives and new possible answers. © 2011 International Association of Scientists in the Interdisciplinary Areas and Springer-Verlag Berlin Heidelberg.

Interdisciplinary Sciences: Computational Life Sciences

A compact review on the comparison of conventional and non-conventional interactions on the structural stability of therapeutic proteins

International Journal of Bioinformatics Research and Applications

Distinct role of non-covalent interactions to the function and structural stability of glutaredoxins: a multifunctional redox protein

The role of noncovalent interactions in carbohydrate recognition by aromatic amino acids has long been reported. To develop a molecular understanding of noncovalent interactions in the recognition process, we have examined a series of binary complexes between 3-methylindole (3-MeIn) and sugars. In particular, the geometries and binding affinities of 3-MeIn with α/β-d-glucose, β-d-galactose, α-d-mannose and α/β-l-fucose are obtained using the MP2(full)/6-31G(d,p) and the M06/TZV2D//MP2/6-31G(d,p) level of theories. The conventional hydrogen bonding such as N-H⋯O and C-H⋯O as well as nonconventional O-H⋯π and C-H⋯π type of interactions is, in general, identified as responsible for the moderately strong interaction energies. Large variations in the position-orientations of 3-MeIn with respect to saccharide are noticed, within the same sugar family, as well as across different sugar series. Furthermore, complexes with large differences in their geometries are recognized as capable of exhibiting very similar interaction energies, underscoring the significance of exhaustive conformation sampling, as carried out in the present study. These observations are readily attributed to the differences in the efficiency of the type of interactions enlisted above. The highest and lowest interaction energies, upon inclusion of 50% BSSE correction, are found to be -16.02 and -6.22 kcal mol-1, respectively, for α-d-glucose (1a) and α-l-fucose (5j). While more number of prominent conventional hydrogen bonding contacts remains as a characteristic feature of the strongly bound complexes, the lower end of the interaction energy spectrum is dominated by multiple C-H⋯π interactions. The complexes exhibiting as many as four C-H⋯π contacts are identified in the case of α/β-d-glucose, β-d-galactose, and α/β-l-fucose with an interaction energy hovering around -8 kcal mol-1. The presence of effective C-H⋯π interactions is found to be dependent on the saccharide configuration as well as the area of the apolar patch constituted by the C-H groups. The study offers a comprehensive set of binary complexes, across different saccharides, which serves as an illustration of the significance and ubiquitous nature of C-H⋯π interactions in carbohydrate binding in saccharide-protein complexes. © 2011 the Owner Societies.

Physical Chemistry Chemical Physics

Quantification of binding affinities of essential sugars with a tryptophan analogue and the ubiquitous role of C-H⋯π interactions

ChemInform

ChemInform Abstract: The CH/π Interaction. Implications in Molecular Recognition

Journal of Theoretical Biology

Role of cation–π interactions in single chain ‘all-alpha’ proteins

Progress in Biophysics and Molecular Biology

Inter-residue interactions in protein folding and stability

International Journal of Biological Macromolecules

Structural analysis of cation–π interactions in DNA binding proteins

Nucleic Acids Research

NCI: a server to identify non-canonical interactions in protein structures

Exploring the Role of C–H….π Interactions on the Structural Stability of Single Chain “All-Alpha” Proteins

Journal	Data powered by TypesetApplied Biochemistry and Biotechnology
Publisher	Data powered by TypesetSpringer Science and Business Media LLC
ISSN	0273-2289
Open Access	0