Insights into the induced fit mechanism in antithrombin–heparin interaction using molecular dynamics simulations

Application of drug discovery software to the identification of heparin-binding sites on protein surfaces: a computational survey of the 4-helix cytokines

“…2 Residues containing atoms within 3.5 Å of ligand in the 5 lowest energy complexes ... [1] ... [3] Page 17 of 34 http://mc.manuscriptcentral.com/tandf/jenmol 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 2 Residues containing atoms within 3.5 Å of ligand in the 5 lowest energy complexes Table 3: Prediction of heparin binding to the interferon/IL10 group of 4-helical cytokines. ... [7] ... [19] ... [15] ... [20] ... [18] ... [17] ... [21] ... [5] ... [22] ... [6] ... [16] ... [13] ... [24] ... [8] ... [25] ... [23] ... [14] ... [26] ... [9] ... [27] ... …”

“…For glycosaminoglycan-protein interactions this course of action is not yet practicable. For one thing, the detailed modelling of GAG ligands with proteins is technically challenging [19], and secondly, the definition of a binding motif in heparin or heparan sulfate in terms of its sequence is problematic, as described above. In addition, heparin and its fragments do not bind tightly to deep clefts in the protein surface, but to superficial sites, and the complexes are formed largely by electrostatic interactions.…”

Differential Effect of Solution Conditions on the Conformation of the Actinoporins Sticholysin II and Equinatoxin II

“…To overcome this limitation, the flexibility and helical content of EqtxII and StnII as a function of both time and residue numbers were evaluated by root mean square fluctuation (RMSF) and ellipticity at 222 nm ( Figure 5), as previously described (Pol-Fachin et al 2009, Terra et al 2007, Verli and Guimarães 2005. The respective plots were drawn from the compilation of average data at every 200 ps of trajectory.…”

Computational Methods for Studying Serpin Conformational Change and Structural Plasticity

“…The simulations indicated that the Z mutation (E342K) affects the local hydrogen bonding and salt-bridging network, leading to conformational and dynamical deviations when compared to the wild type. Later on, the induced fit mechanism of antithrombin activation by heparin was studied by Verli and Guimaraes (2005). MD simulations of heparinbound and unbound antithrombin were performed in order to understand the binding of heparin and its global effect on antithrombin conformation.…”