PMID- 30959812
OWN - NLM
STAT- MEDLINE
DCOM- 20190726
LR  - 20200225
IS  - 1420-3049 (Electronic)
IS  - 1420-3049 (Linking)
VI  - 24
IP  - 7
DP  - 2019 Apr 5
TI  - In Silico Peptide Ligation: Iterative Residue Docking and Linking as a New 
      Approach to Predict Protein-Peptide Interactions.
LID - 10.3390/molecules24071351 [doi]
LID - 1351
AB  - Peptide(-)protein interactions are corner-stones of living functions involved in 
      essential mechanisms, such as cell signaling. Given the difficulty of obtaining 
      direct experimental structural biology data, prediction of those interactions is 
      of crucial interest for the rational development of new drugs, notably to fight 
      diseases, such as cancer or Alzheimer's disease. Because of the high flexibility 
      of natural unconstrained linear peptides, prediction of their binding mode in a 
      protein cavity remains challenging. Several theoretical approaches have been 
      developed in the last decade to address this issue. Nevertheless, improvements 
      are needed, such as the conformation prediction of peptide side-chains, which are 
      dependent on peptide length and flexibility. Here, we present a novel in silico 
      method, Iterative Residue Docking and Linking (IRDL), to efficiently predict 
      peptide(-)protein interactions. In order to reduce the conformational space, this 
      innovative method splits peptides into several short segments. Then, it uses the 
      performance of intramolecular covalent docking to rebuild, sequentially, the 
      complete peptide in the active site of its protein target. Once the peptide is 
      constructed, a rescoring step is applied in order to correctly rank all IRDL 
      solutions. Applied on a set of 11 crystallized peptide(-)protein complexes, the 
      IRDL method shows promising results, since it is able to retrieve experimental 
      binding conformations with a Root Mean Square Deviation (RMSD) below 2 A in the 
      top five ranked solutions. For some complexes, IRDL method outperforms two other 
      docking protocols evaluated in this study. Hence, IRDL is a new tool that could 
      be used in drug design projects to predict peptide(-)protein interactions.
FAU - Diharce, Julien
AU  - Diharce J
AD  - Institut de Chimie Organique et Analytique (ICOA), UMR CNRS-Universite d'Orleans 
      7311, Universite d'Orleans BP 6759, 45067, Orleans CEDEX 2, France. 
      julien.diharce@univ-orleans.fr.
FAU - Cueto, Mickael
AU  - Cueto M
AD  - Institut de Chimie Organique et Analytique (ICOA), UMR CNRS-Universite d'Orleans 
      7311, Universite d'Orleans BP 6759, 45067, Orleans CEDEX 2, France. 
      mickael.cueto@etu.univ-orleans.fr.
FAU - Beltramo, Massimiliano
AU  - Beltramo M
AD  - UMR Physiologie de la Reproduction et des Comportements (INRA, UMR85; CNRS, 
      UMR7247; Universitede Tours; IFCE), F-37380 Nouzilly, France. 
      massimiliano.beltramo@inra.fr.
FAU - Aucagne, Vincent
AU  - Aucagne V
AD  - Centre de Biophysique Moleculaire (CNRS UPR4301), Rue Charles Sadron, F-45071 
      Orleans cedex 2, France. massimiliano.beltramo@inra.fr.
FAU - Bonnet, Pascal
AU  - Bonnet P
AD  - Institut de Chimie Organique et Analytique (ICOA), UMR CNRS-Universite d'Orleans 
      7311, Universite d'Orleans BP 6759, 45067, Orleans CEDEX 2, France. 
      pascal.bonnet@univ-orleans.fr.
LA  - eng
GR  - APR-IR 2016/Conseil Regional du Centre-Val de Loire/
GR  - ANR KISS ANR-15-CE20-0015/Agence Nationale de la Recherche/
GR  - REPiCGO/Canceropole Grand Ouest/
PT  - Journal Article
DEP - 20190405
PL  - Switzerland
TA  - Molecules
JT  - Molecules (Basel, Switzerland)
JID - 100964009
RN  - 0 (Peptides)
RN  - 0 (Proteins)
MH  - Binding Sites
MH  - *Biophysical Phenomena
MH  - Computer Simulation
MH  - Humans
MH  - Molecular Docking Simulation
MH  - Peptides/*chemistry/genetics
MH  - Protein Binding
MH  - Protein Conformation
MH  - Protein Interaction Maps/*genetics
MH  - Proteins/*chemistry/genetics
PMC - PMC6480567
OTO - NOTNLM
OT  - covalent docking
OT  - molecular modeling
OT  - peptide conformation
OT  - protein-peptide interaction
COIS- The authors declare no conflict of interest.
EDAT- 2019/04/10 06:00
MHDA- 2019/07/28 06:00
PMCR- 2019/04/05
CRDT- 2019/04/10 06:00
PHST- 2019/01/20 00:00 [received]
PHST- 2019/04/02 00:00 [revised]
PHST- 2019/04/03 00:00 [accepted]
PHST- 2019/04/10 06:00 [entrez]
PHST- 2019/04/10 06:00 [pubmed]
PHST- 2019/07/28 06:00 [medline]
PHST- 2019/04/05 00:00 [pmc-release]
AID - molecules24071351 [pii]
AID - molecules-24-01351 [pii]
AID - 10.3390/molecules24071351 [doi]
PST - epublish
SO  - Molecules. 2019 Apr 5;24(7):1351. doi: 10.3390/molecules24071351.