Covalent Docking in Drug Discovery: Scope and Limitations.

  title={Covalent Docking in Drug Discovery: Scope and Limitations.},
  author={Andrea Scarpino and Gy{\"o}rgy G. Ferenczy and Gy{\"o}rgy Mikl{\'o}s Keserű},
  journal={Current pharmaceutical design},
Drug discovery efforts for new covalent inhibitors have drastically been increased in the last few years. The binding mechanism of covalent compounds entails the formation of a chemical bond between their electrophilic warhead group and the protein of interest. The use of moderately reactive warheads targeting non-conserved nucleophilic residues can improve the affinity and selectivity profiles of covalent binders as compared to their noncovalent analogues. Recent advances have also enabled… 

Covalent docking in CDOCKER

The implementation and testing of a covalent docking methodology in Rigid CDOCKER and the optimization of the corresponding physics-based scoring function with an additional customizable covalENT bond grid potential which represents the free energy change of bond formation between the ligand and the receptor are described.

Reactivity of Covalent Fragments and Their Role in Fragment Based Drug Discovery

The requirements for an electrophilic fragment library and the importance of differing warhead reactivity are discussed and successful case studies from the world of drug discovery are examined.

Modeling receptor flexibility in the structure-based design of KRASG12C inhibitors

These approaches were of significant use in facilitating the structure-based design of KRASG12C inhibitors and are anticipated to be of further use in the design of covalent (and noncovalent) inhibitors of other conformationally labile protein targets.

Advances in computer-aided drug design for type 2 diabetes

This study reviews the applications of CADD in diabetic drug designing by elaborating the discovery, including peroxisome proliferator-activated receptor (PPAR), G protein-coupled receptor 40 (GPR40), dipeptidyl peptidase-IV (DDP-IV), protein tyrosine phosphatase 1B (PTP1B), sodium-dependent glucose transporter 2 (SGLT-2), and glucokinase (GK).

Advanced approaches of developing targeted covalent drugs

This review highlights developing strategies of covalent drug discovery and successful applications to address challenges of designing effective covalent drugs.

Modeling receptor flexibility in the structure‐based design of KRAS inhibitors Kai Zhu1 · Cui Li3 · Kingsley Y. Wu4 · Christopher Mohr1 · Xun Li3 · Brian Lanman2

  • 2022