Side chain flexibility

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

Long side chain Interaction in long side chain Flexible backbone... 

The accessibility component, called , represents the recognition between the specific protein and the ligand when the ligand is positioned in the protein and exposes the atom i to the enzyme anchor point. It depends on the 3D structure, conformation and chirality of the ligand and the 3D structure and side chain flexibility of the enzyme. Thus, the fc) score is proportional to the exposure of the ligand atom i to the anchor point of a specific enzyme. 

Paddison, S. J. and Elliott, J. A. 2006. On the consequences of side chain flexibility and backbone conformation on hydration and proton dissociation in perfluorosulfonic acid membranes. Physical Chemistry Chemical Physics 8 2193-2203. 

ScHNECKE, V., Swanson, C.A., Getzoff, E.D., Tainer, J.A., and Kuhn, LA. Screening a peptidyl database for potential ligands to proteins with side-chain flexibility. Proteins Struct., Func., Genet. 1998, 33, 74—87. 

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

Funct., Genet., 33, 74 (1998). Screening a Peptidyl Database for Potential Ligands to Proteins with Side-Chain Flexibility. 

Flexible Docking with Side-Chain Flexibility... 

In an effort to address this issue, the cooperative binding of antifreeze proteins as well as the role of side chain flexibility (14, 15) has been investigated. However, further complications have arisen with the discovery that different antifreeze proteins bind to separate faces or surfaces of an ice crystal (2). It is not surprising then, that a unified hypothesis centered on the molecular mechanism of action has not been proposed. 

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

Najmanovich R, Kuttner J, Sobolev V, Edehnan M. Side chain flexibility in proteins upon ligand binding. Proteins 2000 39 261-268. 

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. 

KaUblad P, Dean PM. Efficient conformational sampling of local side-chain flexibility. J. Molec. Biol. 2003 326 1651-1665. Sherman W, Day T, Jacobson MP, Friesner RA, Farid R. Novel procedure for modeling ligand/receptor induced fit effects. J. Med. Chem. 2006 49 534-553. 

A partial restriction of side-chain flexibility in retinoic acid (108) was achieved by incorporating portions of the side chain into a benzene ring and a cyclopropane ring (109) (68). 

The shapes of the pressure-area isotherms of monolayers of synthetic polypeptides in the a-helical conformation depend on the nature of the side chain interactions. Poly(y-n-decyl-iu-glutamate), poly(i.-leucine), poly(iu-norleucine), and poly(iu-methionine) show differences related to side chain flexibility and dipolar interactions. Comparison of the isotherms of monolayers of the enantiomorphic and racemic forms of polymers [poly(alanine), poly(y-benzyl-glutamate), poly( /3-benzyl-aspartate), poly( e-benzyloxycarbonyllysine )] similarly show features related to side chain properties. The results support the view that when a monolayer consists of a-helices, the shape of the isotherm depends on the difference between the energies of interaction of parallel and antiparallel molecules. These conclusions are discussed in relation to proteins. 

An instructive experiment is to look at three polymers with rather similar side chains poly(L-leucine), poly(L-norleucine), and poly(L-methionine) to compare their surface properties. Finally as an example of extreme side chain flexibility we consider poly(y-n-decyl-L-glutamate), which while quite unlike any protein (more like fat bacon), its surface properties are of some interest and perhaps help us to understand the properties of more protein-like molecules. 

There are now a wide range of methods available to detect domains with amphipathic helicial characteristics at the residue level. However, new methods for describing the amphipathic nature of protein segments at the atomic level are still under development. Attempts to incorporate atomic hydrophobicity values (Cornette et ai, 1987 Tanford, 1978) in describing the amphipathic nature of peptides or other molecules have been described (Eisenberg and McLachlan, 1986). In the future, however, side-chain flexibility, effective solvent-accessible surfaces, electrostatics, and molecular dynamics will have to be included to obtain an accurate description of the amphipathic nature of these protein fragments at an atomic level. 

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