Flexible Docking of Peptide Ligands to Proteins

Desmet, Jan; Maeyer, Marc De; Spriet, J.A.; Lasters, Ignace

doi:10.1385/1-59259-368-2:359

Cited by 4 publications

(5 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As there was no previously reported accuracy for MHC class II peptide modeling, no benchmarking could be performed on the modeled MHC class II peptides. It is notable that validation process by Rognan (Rognan et al 1999), Desmet (Desmet et al 2000), and Sezerman (Sezerman et al 1996) involved remodeling peptides back into their original crystal structure. Using this criterion, our procedure is either comparable or outperforms the three earlier studies (Sezerman et al 1996; Rognan et al 1999; Desmet et al 2000) in terms of the Cα RMSD of the modeled peptides.…”

Section: Resultsmentioning

confidence: 99%

“…The experimental identification of T‐cell epitopes is a time‐consuming and expensive process due to the large number and diverse nature of MHC alleles and candidate peptides. Current computational techniques focus on the identification of potential MHC‐binding candidate peptides, and can be broadly classified into two categories: (1) sequence‐based approaches such as sequence motifs (Falk et al 1991), matrix models (Parker et al 1994; Davenport et al 1995; Gulukota et al 1997; Godkin et al 1998; Rammensee et al 1999), Artificial Neural Network (Brusic et al 1998), Hidden Markov Model (Lim et al 1996; Mamitsuka 1998; Brusic et al 2002), and Support Vector Machine (Dönnes and Elofsson 2002; Bhasin and Raghava 2004) for large‐scale screening of potential T‐cell epitopes from protein sequence databanks; and (2) structure‐based approaches such as homology modeling (Lim et al 1996; Michielin et al 2000), protein threading (Altuvia et al 1995), and docking techniques (Caflisch et al 1992; Rosenfeld et al 1993, 1995; Sezerman et al 1996; Rognan et al 1999; Desmet et al 2000; Michielin and Karplus 2002), which utilize three‐dimensional data for the detailed structural analysis of interactions between the MHC and the bound short antigenic peptides. The former are more suitable for large‐scale screening of potential T‐cell epitopes, while the latter are better suited for detailed analysis of short immunogenic regions of antigens.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Modeling the structure of bound peptide ligands to major histocompatibility complex

2004

View full text Add to dashboard Cite

In this article, we present a new technique for the rapid and precise docking of peptides to MHC class I and class II receptors. Our docking procedure consists of three steps: (1) peptide residues near the ends of the binding groove are docked by using an efficient pseudo-Brownian rigid body docking procedure followed by (2) loop closure of the intervening backbone structure by satisfaction of spatial constraints, and subsequently, (3) the refinement of the entire backbone and ligand interacting side chains and receptor side chains experiencing atomic clash at the MHC receptor-peptide interface. The method was tested by remodeling of 40 nonredundant complexes of at least 3.00 Å resolution for which three-dimensional structural information is available and independently for docking peptides derived from 15 nonredundant complexes into a single template structure. In the first test, 33 out of 40 MHC class I and class II peptides and in the second test, 11 out of 15 MHC-peptide complexes were modeled with a C␣ RMSD < 1.00 Å.

show abstract

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Modeling the structure of bound peptide ligands to major histocompatibility complex

2004

View full text Add to dashboard Cite

show abstract

“…Methods utilising structure in predicting sequential and discontinuous epitopes is new when compared to sequence-based approach. Existing structure-based epitope identifying techniques include mutagenesis, competition experiments, free energy scoring function, knowledge-based free energy scoring, protein threading [29,30], homology modelling [31], virtual pockets, rigid/ flexible docking [32][33][34][35][36] and atomistic molecular dynamics simulations. The molecular dynamics modelling technique is fairly new and not many prediction methods and software have been based on it.…”

Section: Structure-based Epitope Predictionmentioning

confidence: 99%

An introduction to epitope prediction methods and software

Yang

2008

Reviews in Medical Virology

174

125

View full text Add to dashboard Cite

In this paper, current prediction methods and algorithms for both T- and B cell epitopes are reviewed, and a comprehensive summary of epitope prediction software and databases currently available online is also provided. This review can offer researchers in this field a sense of direction and insights for future work. However, our main purpose is to introduce clinical and basic biomedical researchers who are not familiar with these biological analysis tools and databases to these online resources and to provide guidance on how to use them effectively.

show abstract

“…Next, we applied the FASTER algorithm45 to determine the energetically best side‐chain packing of the substituted residues (conserved residues were kept fixed). This program has been described in detail before46 and was applied in an unmodified form. All substituted side‐chains in the 3 constructed models could be placed free of interatomic clashes.…”

Section: Methodsmentioning

confidence: 99%

“…The following sequences were docked: YTAVVPLVY for A1, FLSKQYMTL for both A2 and A24, and FPVRPQVPL for B7. The flexible docking algorithm and settings were applied exactly as described before 2, 46. Briefly, all peptide bond lengths and angles were initialized in standard geometry.…”

Section: Methodsmentioning

confidence: 99%

Anchor profiles of HLA‐specific peptides: Analysis by a novel affinity scoring method and experimental validation

Desmet¹,

Meersseman²,

Boutonnet³

et al. 2004

Proteins

Self Cite

View full text Add to dashboard Cite

The study of intermolecular interactions is a fundamental research subject in biology. Here we report on the development of a quantitative structure-based affinity scoring method for peptide-protein complexes, named PepScope. The method operates on the basis of a highly specific force field function (CHARMM) that is applied to all-atom structural representations of peptide-receptor complexes. Peptide side-chain contributions to total affinity are scored after detailed rotameric sampling followed by controlled energy refinement. A de novo approach to estimate dehydration energies was developed, based on the simulation of individual amino acids in a solvent box filled with explicit water molecules. Transferability of the method was demonstrated by its application to the hydrophobic HLA-A2 and -A24 receptors, the polar HLA-A1, and the sterically ruled HLA-B7 receptor. A combined theoretical and experimental study on 39 anchor substitutions in FxSKQYMTx/HLA-A2 and -A24 complexes indicated a prediction accuracy of about two thirds of a log-unit in Kd. Analysis of free energy contributions identified a great role of desolvation and conformational strain effects in establishing a given specificity profile. Interestingly, the method rightly predicted that most anchor profiles are less specific than so far assumed. This suggests that many potential T-cell epitopes could be missed with current prediction methods. The results presented in this work may therefore significantly affect T-cell epitope discovery programs applied in the field of peptide vaccine development.

show abstract

Flexible Docking of Peptide Ligands to Proteins

Cited by 4 publications

References 21 publications

Modeling the structure of bound peptide ligands to major histocompatibility complex

Modeling the structure of bound peptide ligands to major histocompatibility complex

An introduction to epitope prediction methods and software

Anchor profiles of HLA‐specific peptides: Analysis by a novel affinity scoring method and experimental validation

Contact Info

Product

Resources

About