QSD quadratic shape descriptors. 2. Molecular docking using quadratic shape descriptors (QSDock)

Abstract

We present a new shape-based polynomial time algorithm for the rapid docking of rigid ligands into their macromolecular receptors. The method exploits molecular surface complementarity existing between a putative ligand and its receptor protein. Molecular shapes are represented by using a new shape descriptor that is based on local quadratic approximations to the molecular surface. The quadratic shape descriptor is capable of representing a plethora of molecular shapes and is not limited to describing convex or concave regions of molecular surface. A single pair of complementary descriptors is sufficient for computing the transformation matrix that positions a ligand into the receptor site. We demonstrate the capabilities of our algorithm by successfully reproducing the crystallographically determined orientation for a test set of 20 ligand-protein complexes.

Efficient Unbound Docking of Rigid Molecules

“…This technique was improved further in [23,24] and was also applied to unbound docking [25]. Additional algorithms that employ shape complementarity constraints, when searching for the correct association of molecules were also developed [21,13,10]. Some algorithms are designed to handle flexible molecules [28,27,9].…”

Untitled

“…The interaction of a drug molecule with its receptor protein is a complex event encompassing the interplay in entropy and enthalpy of many forces: conformational flexibility and electrostatic, hydrophobic, and van der Waals interactions 17 . Since the bioactive conformation of a bound ligand rarely corresponds to the isolated ligand X-ray structure, recent techniques have dealt with the issue of conformational flexibility 18 .…”

Descriptor-based Fitting of Structurally Diverse LPA1 Inhibitors into a Single predictive Mathematical Model

“…Ligand-based approach depends on at least one known active compound; which serves as the query for searching library of compounds using predefined molecular descriptor parameters [1,2]. Three categories of chemical descriptors have been characterized till date; physical properties descriptors (1D-descriptor), molecular topology and pharmacophore descriptors (2D-descriptors) and geometrical descriptors (3D-descriptors, often requires prior knowledge of target protein binding-pocket) [3][4][5]. When there are multiple bioactive compounds for a given target, quantitative structure activity relationships (QSARs) method is more beneficial.…”