Molecular dynamics analysis of a buckyball–antibody complex

Abstract

This is a multinanosecond molecular dynamics study of a bio-nano complex formed by a carbon nanoparticle, a buckyball C60, and a biological molecule, an antibody, with high binding affinity and specificity. In the simulation, the ball is completely desolvated by the binding site of the antibody by means of a nearly perfect shape complementarity and extensive side-chain interactions, with the exception that about 17% of the surface is persistently exposed to solvent and could be used for functional derivatization. The interactions are predominantly hydrophobic, but significant polar interactions occur as well. There exists a rich body of various -stacking interactions. Aromatic side chains are involved in both double and triple stackings with the ball. Some ionic side chains, such as the guanidinium group of arginine, also form -stackings with the ball. The results suggest that -stackings are very efficient and common modes of biological recognition of -electron-rich carbon nanoparticles. Most importantly, the results demonstrate that, in general, an ordinary protein binding site, such as that of an antibody, can readily bind to a carbon nanoparticle with high affinity and specificity through recognition modes that are common in protein-ligand recognition. molecular dynamics simulation ͉ molecular recognition ͉ bio-nano conjugate ͉ -stackings I n 1985, a third allotropic form of carbon was discovered (1). The molecule was named Buckministerfullerene, commonly known as the buckyball, because of its geodesic structure (2). Six years later, the fullerene family was expanded with the discovery of nanotubes (3). Because of the unique structural properties associated with these molecules (4), there is great interest in using them in real-world applications (5-9), including integrating nanoparticles into biological systems, a fast-emerging field known as bio-nanotechnology. Examples of potential applications in bio-nanotechnology are transporting devices for drug delivery (10, 11), carriers of radioactive agents for biomedical imaging (12, 13), and templates for designing pharmaceutical agents, such as HIV type 1 protease inhibitors (8, 9), antioxidant (14-16), chemotactic agents (17), and neuroprotectants (18).However, to introduce artificial nanomaterials into living cells, one must deal with issues such as water solubility, biocompatibility, and biodegradability. This requires a comprehensive understanding of the interactions of nanomaterials with biological molecules such as proteins, nucleic acids, membrane lipids, and even water molecules. As in the studies of protein interactions (19,20), computer simulation techniques are very useful to investigate the interfacial properties of bio-nano systems, especially the dynamic, thermodynamic, and mechanical properties, at different spatial and temporal resolutions (21,22). One particularly interesting subject is the study of the interactions of nanoparticles within the binding sites of proteins, and optimizing the interactions for improved bio-nano recognition.Recent bio...

Modeling and simulation of protein–surface interactions: achievements and challenges

“…To alter the hydrophobicity, surface modifications with surface defects and polar groups have been suggested, but these affect the stability of the materials as well as their mechanical and electrical properties (Scida et al 2011). Computational studies of protein-carbon surface interactions have mostly focused on graphene/graphite (Mereghetti & Wade, 2011;Mücksch & Urbassek, 2011;Raffaini & Ganazzoli, 2010;Kang et al 2013;Sun et al 2014b;Yu et al 2012b), CNT (Balamurugan et al 2010;Chen et al 2009b;Tallury & Pasquinelli, 2010;Wang et al 2003) and fullerenes (Durdagi et al 2008;Kraszewski et al 2010;Noon et al 2002).…”

Dynamics of C60Molecules in Biological Membranes: Computer Simulation Studies

“…[24][25][26][27][28][29][30][31] Computer simulation studies for the interaction between carbon nanoparticles and biological materials such as proteins and DNA have also been performed. [32][33][34][35][36][37][38] The inhibition of the HIV-1 protease by fullerenes and their derivatives 32,[36][37] was studied and the binding behavior of carbon nanotubes with nucleic acids 34,38 or amylose 33 was also investigated to improve the solubility of nanotubes. Recently, Srinivas and Klein 39 studied the interaction between a synthetic nanotube and a DMPC lipid bilayer using molecular dynamics simulations of a coarsegrained (CG) model.…”

Nanotoxicity: Exploring the Interactions Between Carbon Nanotubes and Proteins

“…To validate this prediction from our in silico approach, in vitro and/or in vivo experiments are highly needed. Interestingly, there is recent evidence from both experiment and theory showing that some antibody from mouse immune repertoire can "absorb" the C60 nanoparticle through similar hydrophobic interactions [75,76].…”