A Computational and Experimental Analysis of Ligand Binding to Type 1 Collagen

J.      Vaidyanathan; T.   K.   Vaidyanathan; N.      Ramasubbu; S.      Ravichandran

Abstract

Type 1 collagen is the primary protein in extracellular matrix of major tissues. Ligand binding to type 1 collagen is therefore an important problem of interest in areas such as adhesive bonding to tissues, mineralization of collagen scaffolds etc. The triple helical structure of collagen molecule, and the selfassembly of these molecules into fibrils as well as the role of water in its conformational state present interesting challenges in evaluating the binding of ligands to such a structure. Computer simulation of interactions between collagen and other molecular entities (e.g., ligands, proteins, mineral entities etc.) can provide a wealth of information. This paper reviews the computational methods suitable for applications to collagen-ligand binding studies and the current literature on such studies. These methods have been used for indirect (active analog approach) and direct (manual and automatic docking) methods of computer binding simulations. In particular, AutoDock method was extremely valuable to identify the low energy collagenligand complexes, to visualize the hydrogen bonds between collagen and ligands in their complexes, and to characterize the docking/binding energy parameters in the presence of water. Experimental binding assay studies were also used to characterize the interactions. The results give valuable information on criteria for formulation design in practical applications of adhesive bonding to tissues (e.g., bonding of dentin prior to filling of cavities to treat caries). Ongoing current studies also focus on immobilization of charged protein molecules on type 1 collagen to aid in biomimetic mineralization of collagen scaffolds.

Keywords: docking simulation, ligand binding, collagen target, autodock, scoring

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