Abstract:
:Starting from the X-ray structure of a class I major histocompatibility complex (MHC)-encoded protein (HLA-B*2705), a naturally presented self-nonapeptide and two synthetic analogues were simulated in the binding groove of two human leukocyte antigen (HLA) alleles (B*2703 and B*2705) differing in a single amino acid residue. After 200 ps molecular dynamics simulations of the solvated HLA-peptide pairs, some molecular properties of the complexes (distances between ligand and protein center of masses, atomic fluctuations, buried versus accessible surface areas, hydrogen-bond frequencies) allow a clear discrimination of potent from weak MHC binders. The binding specificity of the three nonapeptides for the two HLA alleles could be explained by the disruption of one hydrogen-bonding network in the binding pocket of the HLA-B*2705 protein where the single mutation occurs. Rearrangements of interactions in the B pocket, which binds the side chain of peptide residue 2, and a weakening of interactions involving the C-terminal end of the peptide also took place. In addition, extension of the peptide backbone using a beta-Ala analogue did not abolish binding to any of the two HLA-B27 subtypes, but increased the selectivity for B*2703, as expected from the larger peptide binding groove in this subtype. A better understanding of the atomic details involved in peptide selection by closely related HLA alleles is of crucial importance for unraveling the molecular features linking particular HLA alleles to autoimmune diseases, and for the identification of antigenic peptides triggering such pathologies.
journal_name
J Comput Aided Mol Desjournal_title
Journal of computer-aided molecular designauthors
Rognan D,Krebs S,Kuonen O,Lamas JR,López de Castro JA,Folkers Gdoi
10.1023/a:1007963901092subject
Has Abstractpub_date
1997-09-01 00:00:00pages
463-78issue
5eissn
0920-654Xissn
1573-4951journal_volume
11pub_type
杂志文章abstract::An empirical hydrophobic field-like 3D function has been calculated with the program HINT (hydrophobic interactions) and imported into the SYBYL implementation of CoMFA (Comparative Molecular Field Analysis). The addition of hydrophobicity appears to offer increased chemical interpretability of CoMFA models. An exampl...
journal_title:Journal of computer-aided molecular design
pub_type: 杂志文章
doi:10.1007/BF00135313
更新日期:1991-12-01 00:00:00
abstract::Multipoint interactions between synthetic and natural polymers provide a promising platform for many topical applications, including therapeutic blockage of virus-specific targets. Docking may become a useful tool for modelling of such interactions. However, the rigid docking cannot be correctly applied to synthetic p...
journal_title:Journal of computer-aided molecular design
pub_type: 杂志文章
doi:10.1007/s10822-012-9621-7
更新日期:2012-12-01 00:00:00
abstract::We developed a new structure-based in-silico screening method using a negative image of a ligand-binding pocket and a multi-protein-compound interaction matrix. Based on the structure of the ligand pocket of the target protein, we designed a negative image, which consists of virtual atoms whose radii are close to thos...
journal_title:Journal of computer-aided molecular design
pub_type: 杂志文章
doi:10.1007/s10822-006-9047-1
更新日期:2006-04-01 00:00:00
abstract::A linear quantitative-structure activity relationship model is developed in this work using Multiple Linear Regression Analysis as applied to a series of 51 1-(3,3-diphenylpropyl)-piperidinyl phenylacetamides derivatives with CCR5 binding affinity. For the selection of the best variables the Elimination Selection-Step...
journal_title:Journal of computer-aided molecular design
pub_type: 杂志文章
doi:10.1007/s10822-006-9038-2
更新日期:2006-02-01 00:00:00
abstract::This paper describes several case studies concerning protein function inference from its structure using our novel approach described in the accompanying paper. This approach employs family-specific motifs, i.e. three-dimensional amino acid packing patterns that are statistically prevalent within a protein family. For...
journal_title:Journal of computer-aided molecular design
pub_type: 杂志文章
doi:10.1007/s10822-009-9277-0
更新日期:2009-11-01 00:00:00
abstract::Aromatic amino acid residues are often present in carbohydrate-binding sites of proteins. These binding sites are characterized by a placement of a carbohydrate moiety in a stacking orientation to an aromatic ring. This arrangement is an example of CH/pi interactions. Ab initio interaction energies for 20 carbohydrate...
journal_title:Journal of computer-aided molecular design
pub_type: 杂志文章
doi:10.1007/s10822-005-9033-z
更新日期:2005-12-01 00:00:00
abstract::Many molecular simulation methods use force fields to help model and simulate molecules and their behavior in various environments. Force fields are sets of functions and parameters used to calculate the potential energy of a chemical system as a function of the atomic coordinates. Despite the widespread use of force ...
journal_title:Journal of computer-aided molecular design
pub_type: 杂志文章
doi:10.1007/s10822-020-00367-1
更新日期:2021-01-28 00:00:00
abstract::Crystal structures of the 1,4-dihydropyridine (1,4-DHP) calcium channel activators Bay K 8643 [methyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(3-nitrophenyl)-pyridine-5-carboxy lat e], Bay O 8495 [methyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(3-trifluoromethylphenyl)-pyridine-5- carboxylate], and Bay O 9507 [methyl 1,4-dihydr...
journal_title:Journal of computer-aided molecular design
pub_type: 杂志文章
doi:10.1007/BF00129749
更新日期:1991-04-01 00:00:00
abstract::Formyl-peptide receptors (FPRs) belong to the family A of the G-protein coupled receptor superfamily and include three subtypes: FPR, FPR-like-1 and FPR-like-2. They have been involved in the control of many inflammatory processes promoting the recruitment and infiltration of leukocytes in regions of inflammation thro...
journal_title:Journal of computer-aided molecular design
pub_type: 杂志文章
doi:10.1007/s10822-006-9055-1
更新日期:2006-05-01 00:00:00
abstract::The design of molecules with desired properties is still a challenge because of the largely unpredictable end results. Computational methods can be used to assist and speed up this process. In particular, genetic algorithms have proved to be powerful tools with a wide range of applications, e.g. in the field of drug d...
journal_title:Journal of computer-aided molecular design
pub_type: 杂志文章
doi:10.1023/a:1021928016359
更新日期:2002-08-01 00:00:00
abstract::Poly(amidoamine) (PAMAM) dendrimers have been extensively studied as delivery vectors in biomedical applications. A limited number of molecular dynamics (MD) simulation studies have investigated the effect of surface chemistry on therapeutic molecules loading, with the aim of providing insights for biocompatibility im...
journal_title:Journal of computer-aided molecular design
pub_type: 杂志文章
doi:10.1007/s10822-017-0091-9
更新日期:2017-12-01 00:00:00
abstract::Water molecules in the binding pocket of a protein and their role in ligand binding have increasingly raised interest in recent years. Displacement of such water molecules by ligand atoms can be either favourable or unfavourable for ligand binding depending on the change in free enthalpy. In this study, we investigate...
journal_title:Journal of computer-aided molecular design
pub_type: 杂志文章
doi:10.1007/s10822-012-9620-8
更新日期:2012-12-01 00:00:00
abstract::Hydrogen bonds are the most specific, and therefore predictable of the intermolecular interactions involved in ligand-protein binding. Given the structure of a molecule, it is possible to estimate the positions at which complementary hydrogen-bonding atoms could be found. Crystal-survey data are used in the design of ...
journal_title:Journal of computer-aided molecular design
pub_type: 杂志文章
doi:10.1023/a:1007900527102
更新日期:1997-05-01 00:00:00
abstract::The complex of adenylate kinase with its transition-state inhibitor has been studied by molecular dynamics simulations in water and in vacuum environments with the GROMOS force field over a period of 300 ps. The adenylate kinase, a member of the nucleotide-binding protein family, was exemplarily chosen for the inspect...
journal_title:Journal of computer-aided molecular design
pub_type: 杂志文章
doi:10.1007/BF00125373
更新日期:1994-08-01 00:00:00
abstract::Thirty-six compounds, representing six different structural classes of insecticides which are known to act at the gamma-aminobutyric acid receptor/chloride ionophore, have been superimposed by methods which maximise the commonality of steric and electrostatic fields. Maximal steric and electrostatic alignment was deri...
journal_title:Journal of computer-aided molecular design
pub_type: 杂志文章
doi:10.1007/BF00141574
更新日期:1993-02-01 00:00:00
abstract::The similarity between Plasmodium falciparum phosphodiesterase enzymes (PfPDEs) and their human counterparts have been examined and human PDE9A was found to be a suitable template for the construction of homology models for each of the four PfPDE isoforms. In contrast, the architecture of the active sites of each mode...
journal_title:Journal of computer-aided molecular design
pub_type: 杂志文章
doi:10.1007/s10822-011-9458-5
更新日期:2011-08-01 00:00:00
abstract::Macroscopic pKa values were calculated for all compounds in the SAMPL6 blind prediction challenge, based on quantum chemical calculations with a continuum solvation model and a linear correction derived from a small training set. Microscopic pKa values were derived from the gas-phase free energy difference between pro...
journal_title:Journal of computer-aided molecular design
pub_type: 杂志文章
doi:10.1007/s10822-018-0138-6
更新日期:2018-10-01 00:00:00
abstract::Affinity chromatography is one of the most common techniques employed at the industrial-scale for antibody purification. In particular, the purification of human immunoglobulin G (hIgG) has gained relevance with the immobilization of its natural binding counterpart-Staphylococcus aureus Protein A (SpA) or with the rec...
journal_title:Journal of computer-aided molecular design
pub_type: 杂志文章
doi:10.1007/s10822-013-9703-1
更新日期:2014-01-01 00:00:00
abstract::Capacity ratio (log k') values, which are a measure of hydrophobicity, were calculated directly from the three-dimensional structures of 17 furans and 54 triazines using the comparative molecular field analysis approach. The H2O probe and the GRID force field, including hydrogen-bond potentials, yielded excellent corr...
journal_title:Journal of computer-aided molecular design
pub_type: 杂志文章
doi:10.1007/BF00125172
更新日期:1995-08-01 00:00:00
abstract::Aligning and overlaying two or more bio-active molecules is one of the key tasks in computational drug discovery and bio-activity prediction. Especially chemical-functional molecule characteristics from the view point of a macromolecular target represented as a 3D pharmacophore are the most interesting similarity meas...
journal_title:Journal of computer-aided molecular design
pub_type: 杂志文章
doi:10.1007/s10822-006-9078-7
更新日期:2006-12-01 00:00:00
abstract::The interaction mechanism of triazolyl substituted tetrahydrobenzofuran derivatives (compound 1 (N, N-Dipropyl-1-(2-phenyl-4,5,6,7-tetrahydrobenzofuran-4-yl)-1H-1,2,3-triazole-4-methanamine) and 2 (1-(2-Phenyl-4,5,6,7-tetrahydrobenzofuran-4-yl)-4-(morpholin-4-ylmethyl)-1H-1,2,3-triazole)) with H(+),K(+)-ATPase at diff...
journal_title:Journal of computer-aided molecular design
pub_type: 杂志文章
doi:10.1007/s10822-015-9886-8
更新日期:2016-01-01 00:00:00
abstract::In virtual drug screening, the chemical diversity of hits is an important factor, along with their predicted activity. Moreover, interim results are of interest for directing the further research, and their diversity is also desirable. In this paper, we consider a problem of obtaining a diverse set of virtual screenin...
journal_title:Journal of computer-aided molecular design
pub_type: 杂志文章
doi:10.1007/s10822-017-0093-7
更新日期:2018-02-01 00:00:00
abstract::Folate receptor α (FRα) is a cell surface, glycophosphatidylinositol-anchored protein which has focussed attention as a therapeutic target and as a marker for the diagnosis of cancer. It has a high affinity for the dietary supplemented folic acid (FOL), carrying out endocytic transport across the cell membrane and del...
journal_title:Journal of computer-aided molecular design
pub_type: 杂志文章
doi:10.1007/s10822-014-9801-8
更新日期:2015-01-01 00:00:00
abstract::The one-dimensional model of Hann et al. (JChem Inf Comput Sci 41(3):856–864) has been extended to include reverse binding and wrap-around interaction modes between the protein and ligand to explore the complete combinatorial matrix of molecular recognition. The cumulative distribution function of the Maxwell–Boltzman...
journal_title:Journal of computer-aided molecular design
pub_type: 杂志文章
doi:10.1007/s10822-013-9683-1
更新日期:2013-09-01 00:00:00
abstract::To rigorously assess the tools and protocols that can be used to understand and predict macromolecular recognition, and to gain more structural insight into three newly discovered allosteric binding sites on a critical drug target involved in the treatment of HIV infections, the Olson and Levy labs collaborated on the...
journal_title:Journal of computer-aided molecular design
pub_type: 杂志文章
doi:10.1007/s10822-014-9709-3
更新日期:2014-04-01 00:00:00
abstract::A new type of shape descriptor is proposed to describe the spatial orientation for non-covalent interactions. It is built from simple, anisotropic Gaussian contributions that are parameterised by 10 adjustable values. The descriptors have been used to fit propensity distributions derived from scatter data stored in th...
journal_title:Journal of computer-aided molecular design
pub_type: 杂志文章
doi:10.1023/a:1008109717641
更新日期:2000-11-01 00:00:00
abstract::The V2 vasopressin renal receptor (V2R), which controls antidiuresis in mammals, is a member of the large family of heptahelical transmembrane (7TM) G protein-coupled receptors (GPCRs). Using the automated GPCR modeling facility available via Internet (http:/(/)expasy.hcuge.ch/swissmod/SWISS-MODEL.+ ++html) for constr...
journal_title:Journal of computer-aided molecular design
pub_type: 杂志文章
doi:10.1023/a:1007969526447
更新日期:1998-05-01 00:00:00
abstract::Bradykinin (BK) is a member of the kinin family, released in response to inflammation, trauma, burns, shock, allergy and some cardiovascular diseases, provoking vasodilatation and increased vascular permeability among other effects. Their actions are mediated through at least two G-protein coupled receptors, B1 a rece...
journal_title:Journal of computer-aided molecular design
pub_type: 杂志文章
doi:10.1007/s10822-015-9890-z
更新日期:2016-01-01 00:00:00
abstract::Steric complementarity is a prerequisite for ligand-receptor recognition; this implies that drugs with a common receptor binding site should possess sterically similar binding surfaces. This principle is used as the basis for an automatic and unbiased method that superposes molecules. One molecule is rotated and trans...
journal_title:Journal of computer-aided molecular design
pub_type: 杂志文章
doi:10.1007/BF00124319
更新日期:1995-12-01 00:00:00
abstract::Accurate and well-curated experimental pKa data of organic acids and bases in both aqueous and non-aqueous media are invaluable in many areas of chemical research, including pharmaceutical, agrochemical, specialty chemical and property prediction research. In pharmaceutical research, pKa data are relevant in ligand de...
journal_title:Journal of computer-aided molecular design
pub_type: 杂志文章
doi:10.1007/s10822-014-9764-9
更新日期:2014-10-01 00:00:00