CABS-dock web server for the flexible docking of peptides to proteins without prior knowledge of the binding site

Abstract

Protein–peptide interactions play a key role in cell functions. Their structural characterization, though challenging, is important for the discovery of new drugs. The CABS-dock web server provides an interface for modeling protein–peptide interactions using a highly efficient protocol for the flexible docking of peptides to proteins. While other docking algorithms require pre-defined localization of the binding site, CABS-dock does not require such knowledge. Given a protein receptor structure and a peptide sequence (and starting from random conformations and positions of the peptide), CABS-dock performs simulation search for the binding site allowing for full flexibility of the peptide and small fluctuations of the receptor backbone. This protocol was extensively tested over the largest dataset of non-redundant protein–peptide interactions available to date (including bound and unbound docking cases). For over 80% of bound and unbound dataset cases, we obtained models with high or medium accuracy (sufficient for practical applications). Additionally, as optional features, CABS-dock can exclude user-selected binding modes from docking search or to increase the level of flexibility for chosen receptor fragments. CABS-dock is freely available as a web server at http://biocomp.chem.uw.edu.pl/CABSdock.

Parallel Evolutionary Optimization Algorithms for Peptide-Protein Docking

“…For the case of global docking we compare results with CABS-dock [11] and pepATTRACT [12]. The preparation of structures was performed using the Rosetta Relax protocol.…”

Optimizing the Amino Acid Sequences of Peptides and Improving Their Specificity of Binding to SH3 Domains of Target Proteins

“…5, along with the 3D structure of HCK SH3 domain (PDB ID: 4HCK), were entered into the CABS-dock web server. 28 CABS-dock performed highly efficient and flexible docking simulation to search for possible binding conformations. The accuracy of docking models was measured by the root-mean-square deviation (RMSD).…”

Potensi Gen Oncoprotein Human Papillomavirus Tipe 16 Sebagai Kandidat Vaksin Kanker Serviks

“…Doking molekular dilakukan menggunakan program Cabsdock. 16 Validasi metode dan juga parameter Cabsdock dilakukan dengan doking ulang enam struktur kristal kompleks MHCpeptida yang diperoleh dari PDB. Dalam tahapan penyiapan struktur MHC, asam amino selain sisi aktif protein tidak dimasukkan pada perhitungan doking molekular.…”

“…Suatu program doking dikatakan baik apabila mampu untuk menghasilkan konformasi peptida dengan nilai simpangan (root mean square deviation, RMSD) tidak lebih dari 3 Å terhadap struktur referensinya (struktur kristal peptida). 16 Dalam penelitian ini, hasil validasi memperlihatkan bahwa nilai RMSD program Cabsdock untuk enam struktur kristal peptida-MHC berada pada rentang antara 0,85 sampai 2,61 Å dengan konformasi peptida hasil doking tersebut berada di binding groove yang sama dengan peptida hasil eksperimen sinar-X. Hal ini menunjukkan bahwa parameter dan metode Cabsdock yang dilakukan memiliki kualitas yang baik.…”

“…Hal ini menunjukkan bahwa parameter dan metode Cabsdock yang dilakukan memiliki kualitas yang baik. 16 Setelah metode dan parameter Cabsdock tervalidasi, kemudian dilakukan doking kandidat vaksin epitop terhadap struktur MHC I (kode PDB 1I4F) dan MHC II (kode PDB 1AQD). Interaksi molekular antara peptida kandidat vaksin dan MHC I/II hasil doking ditunjukkan oleh Gambar 1 dan 2 serta Tabel 3 dan Tabel 4.…”