Quantifying the kinetic paths of flexible biomolecular recognition.
Biomolecular recognition often involves large conformational changes, sometimes even local unfolding. The identification of kinetic pathways has become a central issue in understanding the nature of binding. A new approach is proposed here to study the dynamics of this binding-folding process through the establishment of a path-integral framework on the underlying energy landscape. The dominant kinetic paths of binding and folding can be determined and quantified. The significant coupling between the binding and folding of biomolecules often exists in many important cellular processes. In this case, the corresponding kinetic paths of binding are shown to be intimately correlated with those of folding and the dynamics becomes quite cooperative. This implies that binding and folding happen concurrently. When the coupling between binding and folding is weak (strong), the kinetic process usually starts with significant folding (binding) first, with the binding (folding) later proceeding to the end. The kinetic rate can be obtained through the contributions from the dominant paths. The rate is shown to have a bell-shaped dependence on temperature in the concentration-saturated regime consistent with experiment. The changes of the kinetics that occur upon changing the parameters of the underlying binding-folding energy landscape are studied.
Wang
Jin
J
State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, China.
Zhang
Kun
K
Lu
Hongyang
H
Wang
Erkang
E
D001703:Biophysics / Q000379:methods*; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D019277:Entropy; D007700:Kinetics; D015233:Models, Statistical; D008962:Models, Theoretical; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry; D013696:Temperature; D013816:Thermodynamics
D011506:Proteins