Flexible Docking with Side-Chain Flexibility

Flexible Docking with Side-Chain Flexibility 

A series of simulations starting from reverse initial conditions (protein structures in bound conformations with hot-spot residue pairs in unbound rotameric states) leads to impaired contact formation during the initial docking phase. These findings indicate, first, that the hot-spot residues can actively hinder or support contact formation and second, that a side-chain refinement protocol relying on specific side-chain rotameric states may well miss crucial structural detail in the interfacial region. 

From the FTDOCK simulations described above, it is obvious that small localized backbone rearrangements in the protein-protein interface can 

---

Flexible Docking with Side-Chain Flexibility... 

Leach A R 1994. Ligand Docking to Proteins With Discrete Side-chain Flexibility. Journal Of Molecula Biology 235 345-356. 

Schaffer, L. and Verkhivker, G. M. (1998) Predicting structural effects in HIV-1 protease mutant complexes with flexible ligand docking and protein side-chain optimization. Proteins Struct. Fund. Gen. 33,295-310. 

Kaiiys, V. and Gilson, M. K. (2002) Enhanced docking with the mining minima optimizer acceleration and side-chain flexibility../. Comp. Chem. 23,1656-1670. 

Leach, A.R. Ligand docking to proteins with discrete side-chain flexibility. /. Mol. Bio., 1994,235,345-356. 

Cherfils J, Duquerroy S, Janin J. Protein-protein recognition analyzed by docking simulation. Proteins 1991 11 271-280. Zacharias M. Protein-protein docking with a reduced protein model accounting for side chain flexibility. Protein Sci. 2354 12 1271-1282. 

Desmet et al. (291) used a truncated (deadend elimination) search procedure to bind flexible peptides to the MHC I receptor. The translation/rotational space covered 6636 relative orientations and each nonglycine/proline residue of the peptide had 47 main-chain con-formers. Side chains had threefold rotations about their chi angles and 28 side chains of the receptor were allowed to rotate. Seventy-four low energy structures were obtained with an average rmsd of 1 A. The lowest energy structure had an rmsd of 0.56 A. Peptides up to 20 residues were docked with this procedure. 

---