4, 5ĭocking programs generally use a scoring function, that can be seen as an attempt to approximate the standard chemical potentials of the system. It is a qualitatively different concept governed not only by the minima in the energy profile, but also by the shape of the profile and the temperature. Importantly, while molecular dynamics directly deals with energies (referred to as force fields in chemistry), docking is ultimately interested in reproducing chemical potentials, which determine the bound conformation preference and the free energy of binding. ![]() Additionally, docking generally assumes much or all of the receptor rigid, the covalent lengths and angles constant, while considering a chosen set of covalent bonds freely rotatable (referred to as active rotatable bonds here). 3Īmong the assumptions made by these approaches is the commitment to a particular protonation state of and charge distribution in the molecules that do not change between, for example, their bound and unbound states. 2Ĭan be seen as making an increasing trade-off of the representational detail for computational speed. For example, hundreds of thousands of computers are used for running docking in and similar projects. One is interested in maximizing the accuracy of these predictions while minimizing the computer time they take, since the computational resources spent on docking are considerable. ![]() ![]() Docking can also be used to try to predict the bound conformation of known binders, when the experimental holo structures are unavailable. The prediction of binding of small molecules to proteins is of particular practical importance because it is used to screen virtual libraries of drug-like molecules in order to obtain leads for further drug development. The goal is to predict the bound conformations and the binding affinity. Molecular docking is a computational procedure that attempts to predict noncovalent binding of macromolecules or, more frequently, of a macromolecule (receptor) and a small molecule (ligand) efficiently, starting with their unbound structures, structures obtained from MD simulations, or homology modeling, etc.
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