LYRA, a webserver for lymphocyte receptor structural modeling

Abstract

The accurate structural modeling of B- and T-cell receptors is fundamental to gain a detailed insight in the mechanisms underlying immunity and in developing new drugs and therapies. The LYRA (LYmphocyte Receptor Automated modeling) web server (http://www.cbs.dtu.dk/services/LYRA/) implements a complete and automated method for building of B- and T-cell receptor structural models starting from their amino acid sequence alone. The webserver is freely available and easy to use for non-specialists. Upon submission, LYRA automatically generates alignments using ad hoc profiles, predicts the structural class of each hypervariable loop, selects the best templates in an automatic fashion, and provides within minutes a complete 3D model that can be downloaded or inspected online. Experienced users can manually select or exclude template structures according to case specific information. LYRA is based on the canonical structure method, that in the last 30 years has been successfully used to generate antibody models of high accuracy, and in our benchmarks this approach proves to achieve similarly good results on TCR modeling, with a benchmarked average RMSD accuracy of 1.29 and 1.48 Å for B- and T-cell receptors, respectively. To the best of our knowledge, LYRA is the first automated server for the prediction of TCR structure.

Particulate Array of Well-Ordered HIV Clade C Env Trimers Elicits Neutralizing Antibodies that Display a Unique V2 Cap Approach

“…A structural model of the D11A.F9 variable fragment (Fv) was generated from the corresponding aa sequence using three different molecular modeling servers: LYRA (Lymphocyte Receptor Automated Modeling) (Klausen et al, 2015), RaptorX (Kallberg et al, 2012), and Rosetta Antibody Protocol (Lyskov et al, 2013). The Fvs were superimposed using Chimera.…”

Structural Basis for Clonal Diversity of the Public T Cell Response to a Dominant Human Cytomegalovirus Epitope

“…Modeling of TCR⅐NLV⅐HLA-A2 Complexes-Initial structural models of the E4.1 (12) and RA11 (16) TCRs were produced using the Lyra web server (39). We used the Modeler program (40) to remodel the CDR3␣ for both structures using the shared residues from the C25 CDR3␣ (NNNDMR) as a template.…”

Applicability of predictive toxicology methods for monoclonal antibody therapeutics: status Quo and scope

“…Advances made in PCM techniques include a new descriptor for antigen–antibody interaction called epitope–paratope interaction fingerprint (EPIF) which tries to address the higher time-complexity of MLPD, thus allowing for simplification the antigen–antibody interaction term (Qiu et al 2015, 2016). Platforms like proABC, ABangle and LYRA allow for modelling antigen–antibody interactions, orientation of variable chain and lymphocyte receptor, respectively (Klausen et al 2015; Olimpieri et al 2013; Dunbar et al 2013). Physicochemical characteristics of mAbs will influence PK/PD properties (increased binding to serum proteins and increased half-life) which affects ADME characteristics thus impacting bioavailability and biological activity.…”