softsimu
Binding of osteopontin on biomineral calcium oxalate monohydrate (kidney stone): 1. No phosphorylation. Side view
Osteopontin (OPN) is a naturally occurring protein present, for example, in bone and eggshells. Importantly, OPN has been reported to inhibit formation of crystals of calcium oxalate monohydrate (COM), hydroxyapatite and some other biominerals. Of these, COM is the most common mineral in kidney stones.
We used a combination of experimental techniques (scanning confocal microscopy and scanning electron microscopy) and Molecular Dynamics simulations to study how phosphorylation of OPN influences its ability to bind on different faces of COM crystals. The aim is to discover the main binding mechanisms and with that information be able to inhibit the growth of kidney stones and use the same mechanism to control formation of other biominerals.
This simulation shows binding of OPN with no phosphorylation. As the video shows, OPN does not bind well ({100} face of COM) despite the fact that OPN is highly negative and COM has positive surface charge. Please see the movies (link below) with one and three phosphorylations. The differences are remarkable. Binding is, however, mainly electrostatic and phosphorylation is needed to mediate the contacts between OPN and the crystal - OPN is mostly disoredered protein and has no preferred folded pattern on the surface.
See also:
- Interaction of aspartic acid (of osteopontin) with calcium oxalate monohydrate surface
Computational resources:
- SharcNet
References:
1. Control of Calcium Oxalate Crystal Growth by Face-Specific Adsorption of an Osteopontin Phosphopeptide. B. Grohe, J. O'Young, D.A. Ionescu, G. Lajoie, K.A. Rogers, M. Karttunen, H.A. Goldberg, G.K. Hunter, J. Am. Chem. Soc. 129, 14946-14951 (2007).
2. Phosphorylation of osteopontin peptides mediates adsorption to and incorporation into calcium oxalate crystals. O'Young, Jason; Chirico, Sara; Al Tarhuni, Nehal; Grohe, Bernd; Karttunen, Mikko; Goldberg, Harvey A; Hunter, Graeme K. Cells, tissues, organs 189, 51-5 (2009).
3. The flexible polyelectrolyte hypothesis of protein-biomineral interaction. Hunter, G.K., O’Young, J., Grohe, B., Karttunen, M. & Goldberg, H, Langmuir 26, 18639-46 (2010).
Binding of osteopontin on biomineral calcium oxalate monohydrate (kidney stone): 1. No phosphorylation. Side view
Osteopontin (OPN) is a naturally occurring protein present, for example, in bone and eggshells. Importantly, OPN has been reported to inhibit formation of crystals of calcium oxalate monohydrate (COM), hydroxyapatite and some other biominerals. Of these, COM is the most common mineral in kidney stones.
We used a combination of experimental techniques (scanning confocal microscopy and scanning electron microscopy) and Molecular Dynamics simulations to study how phosphorylation of OPN influences its ability to bind on different faces of COM crystals. The aim is to discover the main binding mechanisms and with that information be able to inhibit the growth of kidney stones and use the same mechanism to control formation of other biominerals.
This simulation shows binding of OPN with no phosphorylation. As the video shows, OPN does not bind well ({100} face of COM) despite the fact that OPN is highly negative and COM has positive surface charge. Please see the movies (link below) with one and three phosphorylations. The differences are remarkable. Binding is, however, mainly electrostatic and phosphorylation is needed to mediate the contacts between OPN and the crystal - OPN is mostly disoredered protein and has no preferred folded pattern on the surface.
See also:
- Interaction of aspartic acid (of osteopontin) with calcium oxalate monohydrate surface
Computational resources:
- SharcNet
References:
1. Control of Calcium Oxalate Crystal Growth by Face-Specific Adsorption of an Osteopontin Phosphopeptide. B. Grohe, J. O'Young, D.A. Ionescu, G. Lajoie, K.A. Rogers, M. Karttunen, H.A. Goldberg, G.K. Hunter, J. Am. Chem. Soc. 129, 14946-14951 (2007).
2. Phosphorylation of osteopontin peptides mediates adsorption to and incorporation into calcium oxalate crystals. O'Young, Jason; Chirico, Sara; Al Tarhuni, Nehal; Grohe, Bernd; Karttunen, Mikko; Goldberg, Harvey A; Hunter, Graeme K. Cells, tissues, organs 189, 51-5 (2009).
3. The flexible polyelectrolyte hypothesis of protein-biomineral interaction. Hunter, G.K., O’Young, J., Grohe, B., Karttunen, M. & Goldberg, H, Langmuir 26, 18639-46 (2010).