TL;DR: Fast, memory‐efficient and robust execution make this software attractive for applications both in computationally expensive energy minimization algorithms, such as docking or molecular dynamics simulations, and in stand‐alone surface area and curvature calculations.
Abstract: New computer programs, SurfRace and FastSurf, perform fast calculations of the solvent accessible and molecular (solvent excluded) surface areas of macromolecules. Program SurfRace also calculates the areas of cavities inaccessible from the outside. We introduce the definition of average curvature of molecular surface and calculate average molecular surface curvatures for each atom in a structure. All surface area and curvature calculations are analytic and therefore yield exact values of these quantities. High calculation speed of this software is achieved primarily by avoiding computationally expensive mathematical procedures wherever possible and by efficient handling of surface data structures. The programs are written initially in the language C for PCs running Windows 2000/98/NT, but their code is portable to other platforms with only minor changes in input-output procedures. The algorithm is robust and does not ignore either multiplicity or degeneracy of atomic overlaps. Fast, memory-efficient and robust execution make this software attractive for applications both in computationally expensive energy minimization algorithms, such as docking or molecular dynamics simulations, and in stand-alone surface area and curvature calculations.
02 Mar 2011-Bioinformation
TL;DR: In this article, the authors locate the position of these mutations in the AB5 structure to infer complex assembly for its functional role in different serogroups and show that mutations in CTA are at the solvent exposed regions of AB5 complex, whereas those in the CTB/CTB interface of the homo-pentamer complex.
Abstract: Cholera is a global disease that has persisted for millennia The cholera toxin (CT) from Vibrio cholerae is responsible for the clinical symptoms of cholera This toxin is a hetero-hexamer (AB5) complex consisting of a subunit A (CTA) with a pentamer (B5) of subunit B (CTB) The importance of the AB5 complex for pathogenesis is established for the wild type O1 serogroup using known structural and functional data However, its role is not yet documented in other known serogroups harboring sequence level residue mutations The sequences for the toxin from different serogroups are available in GenBank (release 177) Sequence analysis reveals mutations at several sequence positions in the toxin across serogroups Therefore, it is of interest to locate the position of these mutations in the AB5 structure to infer complex assembly for its functional role in different serogroups We show that mutations in the CTA are at the solvent exposed regions of the AB5 complex, whereas those in the CTB are at the CTB/CTB interface of the homo-pentamer complex Thus, the role of mutations at the CTB/CTB interface for B5 complex assembly is implied It is observed that these mutations are often non-synonymous (eg polar to non-polar or vice versa) The formation of the AB5 complex involves inter-subunit residue-residue interactions at the protein-protein interfaces Hence, these mutations, at the structurally relevant positions, are of importance for the understanding of pathogenesis by several serogroups This is also of significance in the improvement of recombinant CT protein complex analogs for vaccine design and their use against multiple serogroups
22 Mar 2011-Bioinformation
TL;DR: Regression analysis shows that blood and brain gp120 and gp41 percent sequence polarity range correlate with mean Shannon entropy, which point to the use of protein modifications to enhance HIV-1 ENV vaccines across multiple clades, blood, and brain.
Abstract: 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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